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  • 1.
    Bergkvist, Anders
    et al.
    Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden / Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, USA.
    Ejdebäck, Mikael
    University of Skövde, Department of Natural Sciences. Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Ubbink, Marcellus
    Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, The Netherlands.
    Karlsson, B. Göran
    Department of Molecular Biotechnology, Chalmers University of Technology, Göteborg, Sweden.
    Surface interactions in the complex between cytochrome f and the E43Q/D44N and E59K/E60Q plastocyanin double mutants as determined by (1)H-NMR chemical shift analysis2001In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 10, no 12, p. 2623-2626Article in journal (Refereed)
    Abstract [en]

    A combination of site-directed mutagenesis and NMR chemical shift perturbation analysis of backbone and side-chain protons has been used to characterize the transient complex of the photosynthetic redox proteins plastocyanin and cytochrome f. To elucidate the importance of charged residues on complex formation, the complex of cytochrome f and E43Q/D44N or E59K/E60Q spinach plastocyanin double mutants was studied by full analysis of the (1)H chemical shifts by use of two-dimensional homonuclear NMR spectra. Both mutants show a significant overall decrease in chemical shift perturbations compared with wild-type plastocyanin, in agreement with a large decrease in binding affinity. Qualitatively, the E43Q/D44N mutant showed a similar interaction surface as wild-type plastocyanin. The interaction surface in the E59K/E60Q mutant was distinctly different from wild type. It is concluded that all four charged residues contribute to the affinity and that residues E59 and E60 have an additional role in fine tuning the orientation of the proteins in the complex.

  • 2.
    Browall, Sarah
    et al.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Backhaus, Erik
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Naucler, Pontus
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden / Department of Infectious Diseases, Karolinska University Hospital, Solna, Sweden.
    Galanis, Ilias
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Sjöström, Karin
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Karlsson, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Berg, Stefan
    Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Luthander, Joachim
    Department of Paediatrics, Karolinska University Hospital, Solna, Sweden.
    Eriksson, Margareta
    Department of Paediatrics, Karolinska University Hospital, Solna, Sweden.
    Spindler, Carl
    Department of Infectious Diseases, Karolinska University Hospital, Solna, Sweden.
    Ejdebäck, Mikael
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Trollfors, Birger
    Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Darenberg, Jessica
    Public Health Agency of Sweden, Solna, Sweden.
    Kalin, Mats
    Department of Infectious Diseases, Karolinska University Hospital, Solna, Sweden.
    Örtqvist, Åke
    Department of Communicable Diseases Control and Prevention, Stockholm County Council, Stockholm, Sweden / Department of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Solna, Sweden.
    Andersson, Rune
    Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Henriques-Normark, Birgitta
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden Dept of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
    Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types2014In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 44, no 6, p. 1646-1657Article in journal (Refereed)
  • 3.
    Dunne, Aisling
    et al.
    Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland.
    Ejdebäck, Mikael
    Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland.
    Ludidi, Phumzile L.
    Department of Biochemistry, University of Cambridge, United Kingdom.
    O'Neill, Luke A. J.
    Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland.
    Gay, Nicholas J.
    Department of Biochemistry, University of Cambridge, United Kingdom.
    Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD882003In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 42, p. 41443-41451Article in journal (Refereed)
    Abstract [en]

    The Toll/interleukin 1 receptor (TIR) domain is a region found in the cytoplasmic tails of members of the Toll-like receptor/interleukin-1 receptor superfamily. The domain is essential for signaling and is also found in the adaptor proteins Mal (MyD88 adaptor-like) and MyD88, which function to couple activation of the receptor to downstream signaling components. Experimental structures of two Toll/interleukin 1 receptor domains reveal a alpha-beta-fold similar to that of the bacterial chemotaxis protein CheY, and other evidence suggests that the adaptors can make heterotypic interactions with both the receptors and themselves. Here we show that the purified TIR domains of Mal and MyD88 can form stable heterodimers and also that Mal homodimers and oligomers are dissociated in the presence of ATP. To identify structural features that may contribute to the formation of signaling complexes, we produced models of the TIR domains from human Toll-like receptor 4 (TLR4), Mal, and MyD88. We found that although the overall fold is conserved the electrostatic surface potentials are quite distinct. Docking studies of the models suggest that Mal and MyD88 bind to different regions in TLRs 2 and 4, a finding consistent with a cooperative role of the two adaptors in signaling. Mal and MyD88 are predicted to interact at a third non-overlapping site, suggesting that the receptor and adaptors may form heterotetrameric complexes. The theoretical model of the interactions is supported by experimental data from glutathione S-transferase pull-downs and co-immunoprecipitations. Neither theoretical nor experimental data suggest a direct role for the conserved proline in the BB-loop in the association of TLR4, Mal, and MyD88. Finally we show a sequence relationship between the Drosophila protein Tube and Mal that may indicate a functional equivalence of these two adaptors in the Drosophila and vertebrate Toll pathways.

  • 4.
    Ejdebäck, Mikael
    Göteborgs Universitet.
    Studies on spinach plastocyanin and mutants: Expression in Escherichia coli, folding and function1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Photosynthesis is a process in which photons from sunlight excite chlorophylls in the thylakoid membranes of plants, algae and cyanobacteria. The photo-oxidised reaction centre chlorophyll P700 is re-reduced by an electron transferred from the soluble, blue copper protein plastocyanin. The oxidised plastocyanin dissociates and binds to the cytochrome b6f complex, where it accepts an electron and a new redox cycle can begin. Plastocyanin has three regions of importance for the interaction with its redox partners, a hydrophobic patch and two acidic (negatively charged) patches. Electrostatic interactions between opposite charges are important for the association and the specificity and stability of the formed complexes.

    In this work the interactions with photosystem 1 and cytochrome c have been studied using mutants of plastocyanin. The mutations introduced in the small acidic patch and position 88 of plastocyanin had small effects on the binding to photosystem 1 as compared to the weak binding reported for mutants in the large acidic patch. The affinity was increased by the Glu60Gln, Glu60Lys and Asp61Lys mutations and a more efficient electron transfer was observed for the Gln88Lys mutation. The association between Pc mutated in the small acidic patch and cytochrome c was weakened and the rearrangement hindered by lysines in positions 59 and 60.

    The development of an efficient expression system for spinach plastocyanin in the bacterium Escherichia coli made it possible to produce sufficient amounts of isotopically labelled plastocyanin for NMR experiments. This technique was used for solving the structure of the complex between plastocyanin and cytochrome f. The hydrophobic patch on plastocyanin binds to an area close to the heme on cytochrome f. Electrostatic interactions between opposite charges on the two proteins are also important. The short distance from the heme to the copper ligand His87 suggests an electron transfer from the heme via Tyr1 or Phe4 on cytochrome f.

    The involvement of specific amino-acid residues in copper binding or folding of plastocyanin has also been examined by site-directed mutagenesis. The copper-binding histidines have been replaced by other amino acids, but no blue protein could be produced. The stability of the different redox forms of copper plastocyanin as well as the zinc protein has also been determined by guanidinium-induced unfolding.

  • 5.
    Ejdebäck, Mikael
    et al.
    University of Skövde, Department of Natural Sciences. Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Bergkvist, Anders
    Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Karlsson, B. Göran
    Deptartment of Molecular Biotechnology, Chalmers University of Technology, Göteborg, Sweden.
    Ubbink, Marcellus
    Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Netherlands.
    Side-chain interactions in the plastocyanin-cytochrome f complex2000In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 39, no 17, p. 5022-5027Article in journal (Refereed)
    Abstract [en]

    Cytochrome f and plastocyanin are redox partners in the photosynthetic electron-transfer chain. Electron transfer from cytochrome f to plastocyanin occurs in a specific short-lived complex. To obtain detailed information about the binding interface in this transient complex, the effects of binding on the backbone and side-chain protons of plastocyanin have been analyzed by mapping NMR chemical-shift changes. Cytochrome f was added to plastocyanin up to 0.3 M equiv, and the plastocyanin proton chemical shifts were measured. Out of approximately 500 proton resonances, 86% could be observed with this method. Nineteen percent demonstrate significant chemical-shift changes and these protons are located in the hydrophobic patch (including the copper ligands) and the acidic patches of plastocyanin, demonstrating that both areas are part of the interface in the complex. This is consistent with the recently determined structure of the complex [Ubbink, M., Ejdebäck, M., Karlsson, B. G., and Bendall, D. S. (1998) Structure 6, 323-335]. The largest chemical-shift changes are found around His87 in the hydrophobic patch, which indicates tight contacts and possibly water exclusion from this part of the protein interface. These results support the idea that electron transfer occurs via His87 to the copper in plastocyanin and suggest that the hydrophobic patch determines the specificity of the binding. The chemical-shift changes in the acidic patches are significant but small, suggesting that the acidic groups are involved in electrostatic interactions but remain solvent exposed. The existence of small differences between the present data and those used for the structure may imply that the redox state of the metals in both proteins slightly affects the structure of the complex. The chemical-shift mapping is performed on unlabeled proteins, making it an efficient way to analyze effects of mutations on the structure of the complex.

  • 6.
    Ejdebäck, Mikael
    et al.
    Göteborgs universitet.
    Karlsson, B. G.
    Effects of codon usage and vector-host combinations on the expression of spinach plastocyanin in Escherichia coli1997In: / [ed] American Society for Biochemistry and Molecular Biology, Bethesda: Federation of American Societies for Experimental Biology , 1997, Vol. 11, no 9, p. A1373-Conference paper (Other academic)
  • 7.
    Ejdebäck, Mikael
    et al.
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Young, Simon
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Samuelsson, Anita
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Karlsson, B. Göran
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Effects of codon usage and vector-host combinations on the expression of spinach plastocyanin in Escherichia coli1997In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 11, no 1, p. 17-25Article in journal (Refereed)
    Abstract [en]

    Spinach plastocyanin has been expressed in Escherichia coli and exported to the periplasmic space. The effects of codon usage, expression system, growth length, and temperature on expression levels in LB medium were investigated. A stretch of codons, rare in E. coli, was identified and replaced with highly expressed codons, increasing the yield by at least 20%. Plastocyanin was more efficiently expressed under the T7 promoter than under the lac promoter. Maximum yields were obtained at 37 degrees C when growing the cells for 16 h after induction. The optimized expression system produced 38 mg holoprotein per liter culture. In this system it was also possible to express plastocyanin in minimal medium, at a yield of 10 mg per liter. N-terminal sequencing and mass spectrometry showed that plastocyanin was correctly processed. The expressed plastocyanin was purified to homogeneity, as shown by an A278/A597 ratio of 1.0, and together with amino acid analysis and the determination of oxidized and total copper contents, both the absorption coefficients for epsilon 278 and for epsilon 597 were determined to be 4700 M-1 cm-1.

  • 8.
    Handlin, Linda
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Hydbring-Sandberg, Eva
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden .
    Nilsson, Anne
    Swedish Univ Agr Sci, Dept Anim Environm & Hlth, Skara, Sweden .
    Ejdebäck, Mikael
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Göteborgs universitet.
    Jansson, Anna
    Swedish Univ Agr Sci, Dept Anim Nutr & Management, S-75007 Uppsala, Sweden.
    Uvnäs-Moberg, Kerstin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Short-Term Interaction between Dogs and Their Owners: Effects on Oxytocin, Cortisol, Insulin and Heart Rate-An Exploratory Study2011In: Anthrozoos, ISSN 0892-7936, E-ISSN 1753-0377, Vol. 24, no 3, p. 301-315Article in journal (Refereed)
    Abstract [en]

    The aim of this exploratory study was to determine heart rate and the levels of oxytocin, cortisol, and insulin in dogs and their owners in response to a short-term interaction. In addition, the dogs' behavior was studied. The owners' responses were compared with those obtained from a control group. Ten female volunteers and their own male Labrador dogs participated in an experiment during which the owner stroked, petted, and talked with her dog during the first 3 minutes. Blood samples were collected from both dog and owner before (0) and at 1, 3, 5, 15, 30, and 60 minutes after the start of the interaction. Blood samples were analyzed by EIA. Heart rate was monitored telemetrically. The data were analyzed using linear mixed models and paired t-tests. The dogs' oxytocin levels were significantly increased 3 minutes after the start of the interaction (p = 0.027). Cortisol levels were significantly increased after 15 and 30 minutes (p = 0.004 and p = 0.022, respectively), and heart rate was significantly decreased after 55 minutes (p = 0.008). The dogs displayed normal behaviors during the experiment. The owners' oxylocin levels peaked between 1 and 5 minutes after interaction (p = 0.026). No such effect was seen in the controls. Cortisol levels displayed a significant decrease at 15 or 30 minutes in both owners and controls, and insulin levels did so at 60 minutes (p = 0.030, p = 0.002 and p = 0.002, p < 0.0001, respectively). Heart rate decreased significantly in the owners at 55 and 60 minutes (p = 0.0008) but not in the controls. In conclusion, short-term sensory interaction between dogs and their owners influences hormonal levels and heart rate. However, further studies need to be performed in order to better understand the effects of interaction between dogs and their owners.

  • 9.
    Handlin, Linda
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences. Department of Animal Environment and Health, Swedish University of Agriculture, Skara, Sweden.
    Jonas, Wibke
    Department of Women and Child Health, Division of Reproductive and Perinatal Health Care, Karolinska Institute, Stockholm, Sweden.
    Petersson, Maria
    Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska University Hospital/Karolinska Institute, Stockholm, Sweden.
    Ejdebäck, Mikael
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Ransjö-Arvidsson, Anna-Berit
    Department of Women and Child Health, Division of Reproductive and Perinatal Health Care, Karolinska Institute, Stockholm, Sweden.
    Nissen, Eva
    University of Skövde, School of Life Sciences. Department of Women and Child Health, Division of Reproductive and Perinatal Health Care, Karolinska Institute, Stockholm, Sweden.
    Uvnäs-Moberg, Kerstin
    University of Skövde, School of Life Sciences. Department of Animal Environment and Health, Swedish University of Agriculture, Skara, Sweden.
    Effects of Sucking and Skin-to-Skin Contact on Maternal ACTH and Cortisol Levels During the Second Day Postpartum - Influence of Epidural Analgesia and Oxytocin in the Perinatal Period2009In: Breastfeeding Medicine, ISSN 1556-8253, E-ISSN 1556-8342, Vol. 4, no 4, p. 207-220Article in journal (Refereed)
    Abstract [en]

    Background and Aims: In this study we made a detailed analysis of the mothers' release pattern of adreno-corticotropic hormone (ACTH) and cortisol during a breastfeeding session during the second day postpartum and related these patterns to maternal oxytocin levels as well to the duration of sucking and the duration of skin-to-skin contact before sucking the breast. Furthermore, we investigated if epidural analgesia and oxytocin administration during and after labor influenced the release pattern of ACTH and cortisol.

    Methods: Sixty-three primiparae were included in the study. Fourteen received oxytocin intramuscularly postpartum, nine received oxytocin infusion, 14 received epidural analgesia combined with oxytocin infusion, and six received epidural analgesia alone. Twenty mothers did not receive any of these medical interventions. Blood samples were analyzed for ACTH and cortisol by enzyme-linked immunoassay.

    Results: Both ACTH and cortisol levels fell significantly during the breastfeeding session. A significant negative relationship was found between oxytocin and ACTH levels, but not between oxytocin and cortisol levels. A contact before onset of sucking was significantly and negatively associated with lower cortisol levels, but not with ACTH levels. Cortisol levels differed significantly between mothers having received epidural analgesia with and without oxytocin.

    Conclusions: Breastfeeding is associated with a decrease of ACTH and cortisol levels. Skin-to-skin contact contributes to this effect. ACTH correlated negatively with the duration of sucking and median oxytocin levels, whereas cortisol levels correlated inversely with the duration of skin-to-skin contact preceding sucking, suggesting a partial dissociation between the mechanisms regulating ACTH and cortisol release. In addition, medical interventions in connection with birth influence the activity of the hypothalamic-pituitary-adrenal axis 2 days after birth.

  • 10.
    Handlin, Linda
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Nilsson, Anne
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Ejdebäck, Mikael
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Hydbring-Sandberg, Eva
    University of Agricultural Sciences, Uppsala.
    Uvnäs-Moberg, Kerstin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Associations between the Psychological Characteristics of the Human-Dog Relationship and Oxytocin and Cortisol Levels2012In: Anthrozoos, ISSN 0892-7936, E-ISSN 1753-0377, Vol. 25, no 2, p. 215-228Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to explore possible correlations between dog owners' relationships with their dogs, as measured with the Monash Dog Owner Relationship Scale (MDORS), and oxytocin and cortisol levels in both the owners and their dogs. Ten female owners of male Labrador Retrievers completed the MDORS. The scores obtained from the single items, subscales, and total score of the MDORS were calculated. Ten blood samples were collected from each dog owner and her dog during a 60-minute interaction. Blood samples were analyzed for oxytocin and cortisol by Enzyme Immuno Assay (EIA) and mean values of oxytocin and cortisol were calculated in both owners and dogs. The MDORS scores obtained were correlated with basal and mean oxytocin and cortisol levels. The correlation analysis revealed some relationships between the scores of items in the MDORS that reflect the character of the dog-owner-relationship and the owners' hormone levels. For example, higher oxytocin levels in the owners were associated with greater frequency in kissing their dogs (rs = 0.864, p = 0.001). Lower cortisol levels in the owners were associated with their perception that it will be more traumatic when their dog dies (rs = -0.730, p = 0.025). The correlation analysis also revealed some relationships between the scores of items in the MDORS and the dogs' hormone levels. For example, greater frequency in owners kissing their dogs was associated with higher oxytocin levels in the dogs (rs = 0.753, p = 0.029). Six items in the subscale Perceived Costs, as well as the subscale itself, correlated significantly with the dogs' oxytocin levels (rs = 0.820, p = 0.007), that is, the lower the perceived cost, the higher the dogs' oxytocin levels. In addition, significant correlations between the oxytocin levels of the owners and the dogs were demonstrated. Possible mechanisms behind these correlations are discussed. In conclusion, the scores of some items and the subscales of the MDORS correlated with oxytocin, and to a lesser extent cortisol, levels in both the owners and dogs.

  • 11.
    Hardy, Matthew P.
    et al.
    Center for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Victoria, Australia / Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, Dublin 2, Ireland.
    Owczarek, Catherine M.
    Center for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
    Jermiin, Lars S.
    School of Biological Sciences and Sydney University Biological Informatics and Technology Center, University of Sydney, New South Wales 2006, Australia.
    Ejdebäck, Mikael
    Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, Dublin 2, Ireland.
    Hertzog, Paul J.
    Center for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
    Characterization of the type I interferon locus and identification of novel genes2004In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 84, no 2, p. 331-345Article in journal (Refereed)
    Abstract [en]

    The human type I interferon (IFN) genes are clustered on human chromosome 9p21 and the mouse genes are located in the region of conserved synteny on mouse chromosome 4. We have identified two novel mouse Ifna genes (Ifna12, Ifna13) and Ifnl2 (IFN-like 2, a homologue of Limitin/IFN-like 1). Another type I IFN gene was designated Ifne1. Mouse Ifne1 was expressed in ovaries and uterus but not in tissues of hematopoietic origin. IFN-epsilon1 has general structural characteristics of a type I IFN. These studies represent the first detailed annotation of the mouse type I IFN locus, and the products of these novel genes may have important functions in reproduction and host defense.

  • 12.
    Ivković-Jensen, Maja M.
    et al.
    Department of Microbiology, University of Iowa, Iowa City, United States / Department of Chemistry, Iowa State University, Ames, United States.
    Ullmann, G. Matthias
    Institut für Kristallographie, Freie Universität Berlin, Germany.
    Crnogorac, Milan M.
    Department of Microbiology, University of Iowa, Iowa City, United States.
    Ejdebäck, Mikael
    Department of Biochemistry and Biophysics, Lundberg Institute, Göteborg University, Sweden.
    Young, Simon
    Department of Biochemistry and Biophysics, Lundberg Institute, Göteborg University, Sweden.
    Hansson, Örjan
    Department of Biochemistry and Biophysics, Lundberg Institute, Göteborg University, Sweden.
    Kostić, Nenad M.
    Department of Microbiology, University of Iowa, Iowa City, United States.
    Comparing the rates and the activation parameters for the forward reaction between the triplet state of zinc cytochrome c and cupriplastocyanin and the back reaction between the zinc cytochrome c cation radical and cuproplastocyanin1999In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 38, no 5, p. 1589-1597Article in journal (Refereed)
    Abstract [en]

    This is a comparative study of the photoinduced (so-called forward) electron-transfer reaction 3Zncyt/pc(II) --> Zncyt+/pc(I), between the triplet state of zinc cytochrome c (3Zncyt) and cupriplastocyanin [pc(II)], and the thermal (so-called back) electron-transfer reaction Zncyt+/pc(I) --> Zncyt/pc(II), between the cation (radical) of zinc cytochrome c (Zncyt+) and cuproplastocyanin [pc(I)], which follows it. Both reactions occur between associated (docked) reactants, and the respective unimolecular rate constants are kF and kB. Our previous studies showed that the forward reaction is gated by a rearrangement of the diprotein complex. Now we examine the back reaction and complare the two. We study the effects of temperature (in the range 273.3-302.9 K) and viscosity (in the range 1.00-17.4 cP) on the rate constants and determine enthalpies (DeltaH), entropies (DeltaS), and free energies (DeltaG) of activation. We compare wild-type spinach plastocyanin, the single mutants Tyr83Leu and Glu59Lys, and the double mutant Glu59Lys/Glu60Gln. The rate constant kB for wild-type spinach plastocyanin and its mutants markedly depends on viscosity, an indication that the back reaction is also gated. The activation parameters DeltaH and DeltaS show that the forward and back reactions have similar mechanisms, involving a rearrangement of the diprotein complex from the initial binding configuration to the reactive configuration. The rearrangements of the complexes 3Zncyt/pc(II) and Zncyt+/pc(I) that gate their respective reactions are similar but not identical. Since the back reaction of all plastocyanin variants is faster than the forward reaction, the difference in free energy between the docking and the reactive configuration is smaller for the back reaction than for the forward reaction. This difference is explained by the change in the electrostatic potential on the plastocyanin surface as Cu(II) is reduced to Cu(I). It is the smaller DeltaH that makes DeltaG smaller for the back reaction than for the forward reaction.

  • 13.
    Ivković-Jensen, Maja M.
    et al.
    Department of Chemistry, Iowa State University, Ames, United States.
    Ullmann, G. Matthias
    Institut für Kristallographie, Freie Universität Berlin, Germany.
    Young, Simon
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Hansson, Örjan
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Crnogorac, Milan M.
    Department of Chemistry, Iowa State University, Ames, United States.
    Ejdebäck, Mikael
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Kostić, Nenad M.
    Department of Chemistry, Iowa State University, Ames, United States.
    Effects of single and double mutations in plastocyanin on the rate constant and activation parameters for the rearrangement gating the electron-transfer reaction between the triplet state of zinc cytochrome c and cupriplastocyanin1998In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 37, no 26, p. 9557-9569Article in journal (Refereed)
    Abstract [en]

    The unimolecular rate constant for the photoinduced electron-transfer reaction 3Zncyt/pc(II) --> Zncyt+/pc(I) within the electrostatic complex of zinc cytochrome c and spinach cupriplastocyanin is kF. We report the effects on kF of the following factors, all at pH 7.0: 12 single mutations on the plastocyanin surface (Leu12Asn, Leu12Glu, Leu12Lys, Asp42Asn, Asp42Lys, Glu43Asn, Glu59Gln, Glu59Lys, Glu60Gln, Glu60Lys, Gln88Glu, and Gln88Lys), the double mutation Glu59Lys/Glu60Gln, temperature (in the range 273.3-302.9 K), and solution viscosity (in the range 1. 00-116.0 cP) at 283.2 and 293.2 K. We also report the effects of the plastocyanin mutations on the association constant (Ka) and the corresponding free energy of association (DeltaGa) with zinc cytochrome c at 298.2 K. Dependence of kF on temperature yielded the activation parameters DeltaH, DeltaS, and DeltaG. Dependence of kF on solution viscosity yielded the protein friction and confirmed the DeltaG values determined from the temperature dependence. The aforementioned intracomplex reaction is not a simple electron-transfer reaction because donor-acceptor electronic coupling (HAB) and reorganizational energy (lambda), obtained by fitting of the temperature dependence of kF to the Marcus equation, deviate from the expectations based on precedents and because kF greatly depends on viscosity. This last dependence and the fact that certain mutations affect Ka but not kF are two lines of evidence against the mechanism in which the electron-transfer step is coupled with the faster, but thermodynamically unfavorable, rearrangement step. The electron-transfer reaction is gated by the slower, and thus rate determining, structural rearrangement of the diprotein complex; the rate constant kF corresponds to this rearrangement. Isokinetic correlation of DeltaH and DeltaS parameters and Coulombic energies of the various configurations of the Zncyt/pc(II) complex consistently show that the rearrangement is a facile configurational fluctuation of the associated proteins, qualitatively the same process regardless of the mutations in plastocyanin. Correlation of kF with the orientation of the cupriplastocyanin dipole moment indicates that the reactive configuration of the diprotein complex involves the area near the residue 59, between the upper acidic cluster and the hydrophobic patch. Kinetic effects and noneffects of plastocyanin mutations show that the rearrangement from the initial (docking) configuration, which involves both acidic clusters, to the reactive configuration does not involve the lower acidic cluster and the hydrophobic patch but involves the upper acidic cluster and the area near the residue 88.

  • 14.
    Jansson, Hanna
    et al.
    University of Skövde, School of Life Sciences.
    Ökvist, Mats
    University of Skövde, School of Life Sciences.
    Ejdebäck, Mikael
    University of Skövde, School of Life Sciences.
    Hansson, Örjan
    University of Skövde, School of Life Sciences.
    Sjölin, Lennart
    University of Skövde, School of Life Sciences.
    The crystal structure of the spinach plastocyanin double mutant G8D/L12E gives insight into its low reactivity towards photosystem 1 and cytochrome F2003In: Biomedica and Biophysica Acta (BBA), ISSN 0005-2728, Vol. 1607, no 2-3, p. 203-210Article in journal (Refereed)
    Abstract [en]

    Plastocyanin (Pc) is a copper-containing protein, which functions as an electron carrier between the cytochrome b(6)f and photosystem 1 (PS1) complexes in the photosynthetic electron transfer (ET) chain. The ET is mediated by His87 situated in the hydrophobic surface in the north region of Pc. Also situated in this region is Leu12, which mutated to other amino acids severely disturbs the ET from cytochrome f and to PS1, indicating the importance of the hydrophobic surface. The crystal structure of the Pc double mutant G8D/L12E has been determined to 2.0 A resolution, with a crystallographic R-factor of 18.3% (R(free)=23.2%). A comparison with the wild-type structure reveals that structural differences are limited to the sites of the mutations. In particular, there is a small but significant change in the hydrophobic surface close to His87. Evidently, this leads to a mismatch in the reactive complex with the redox partners. For PS1 this results in a 20 times weaker binding and an eightfold slower ET as determined by kinetic measurements. The mutations that have been introduced do not affect the optical absorption spectrum. However, there is a small change in the EPR spectrum, which can be related to changes in the copper coordination geometry

  • 15.
    Jonas, W.
    et al.
    Division of Reproductive and Perinatal Heath Care, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Linda M.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences. Department of Animal Environment and Health, Swedish University of Agriculture, Skara, Sweden.
    Nissen, Eva
    University of Skövde, School of Life Sciences. Division of Reproductive and Perinatal Heath Care, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Ejdebäck, Mikael
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Ransjö-Arvidson, A. B.
    Division of Reproductive and Perinatal Heath Care, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Uvnäs-Moberg, Kerstin
    Department of Animal Environment and Health, Swedish University of Agriculture, Skara.
    Effects of Intrapartum Oxytocin Administration and Epidural Analgesia on the Concentration of Plasma Oxytocin and Prolactin, in Response to Suckling During the Second Day Postpartum2009In: Breastfeeding Medicine, ISSN 1556-8253, E-ISSN 1556-8342, Vol. 4, no 2, p. 71-82Article in journal (Refereed)
    Abstract [en]

    Background: Oxytocin and prolactin stimulate milk ejection and milk production during breastfeeding. The aim of the present study was to make a detailed analysis of maternal release of oxytocin and prolactin in response to breastfeeding during the second day postpartum in mothers who had received oxytocin either intravenously for stimulation of labor or intramuscularly for prevention of postpartum hemorrhage and/or epidural analgesia or those who had received no such treatment in connection with birth.

    Methods: In a descriptive comparative study plasma oxytocin and prolactin concentrations were measured in response to suckling during the second day postpartum in women who had received intravenous intrapartum oxytocin (n = 8), intramuscular postpartum oxytocin (n = 13), or epidural analgesia, either with (n = 14) or without (n = 6) intrapartum oxytocin infusion, and women who received none of these interventions (n = 20). Hormone levels were analyzed by enzyme immunoassay.

    Results: All mothers showed a pulsatile oxytocin pattern during the first 10 minutes of breastfeeding. Women who had received epidural analgesia with oxytocin infusion had the lowest endogenous median oxytocin levels. The more oxytocin infusion the mothers had received during labor, the lower their endogenous oxytocin levels were during a breastfeeding during the second day postpartum. A significant rise of prolactin was observed after 20 minutes in all women, but after 10 minutes in mothers having received oxytocin infusion during labor. In all women, oxytocin variability and the rise of prolactin levels between 0 and 20 minutes correlated significantly with median oxytocin and prolactin levels.

    Conclusion: Oxytocin, released in a pulsatile way, and prolactin were released by breastfeeding during the second day postpartum. Oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Furthermore, oxytocin infusion facilitated the release of prolactin. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively.

  • 16.
    Olesen, K.
    et al.
    Göteborgs universitet.
    Ejdebäck, Mikael
    Göteborgs universitet.
    Hansson, Örjan
    Electron transfer from genetically modified plastocyanin to photosystem 11998In: Photosynthesis: Mechanisms and effects / [ed] Garab, G., Dordrecht: Kluwer Academic Publishers, 1998, p. 1597-1600Conference paper (Other academic)
  • 17.
    Olesen, Kenneth
    et al.
    Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Ejdebäck, Mikael
    University of Skövde, Department of Natural Sciences. Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Crnogorac, Milan M.
    Department of Chemistry, Iowa State University, Ames, United States.
    Kostić, Nenad M.
    Department of Chemistry, Iowa State University, Ames, United States.
    Hansson, Örjan
    Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Electron transfer to photosystem 1 from spinach plastocyanin mutated in the small acidic patch: ionic strength dependence of kinetics and comparison of mechanistic models1999In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 38, no 50, p. 16695-16705Article in journal (Refereed)
    Abstract [en]

    A set of plastocyanin (Pc) mutants, probing the small acidic patch (Glu59, Glu60, and Asp61) and a nearby residue, Gln88, has been constructed to provide further insight into the electron transfer process between Pc and photosystem 1. The negatively charged residues were changed into their neutral counterparts or to a positive lysine. All mutant proteins exhibited electron transfer kinetics qualitatively similar to those of the wild type protein over a wide range of Pc concentrations. The kinetics were slightly faster for the Gln88Lys mutant, while they were significantly slower for the Glu59Lys mutant. The data were analyzed with two different models: one involving a conformational change of the Pc-photosystem 1 complex that precedes the electron transfer step (assumed to be irreversible) [Bottin, H., and Mathis, P. (1985) Biochemistry 24, 6453-6460] and another where no conformational change occurs, the electron transfer step is reversible, and dissociation of products is explicitly taken into account [Drepper, F., Hippler, M., Nitschke, W., and Haehnel, W. (1996) Biochemistry 35, 1282-1295]. Both models can account for the observed kinetics in the limits of low and high Pc concentrations. To discriminate between the models, the effects of added magnesium ions on the kinetics were investigated. At a high Pc concentration (0.7 mM), the ionic strength dependence was found to be consistent with the model involving a conformational change but not with the model where the electron transfer is reversible. One residue in the small acidic patch, Glu60, seems to be responsible for the major part of the ionic strength dependence of the kinetics.

  • 18.
    O'Neill, Luke A. J.
    et al.
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Dunne, Aisling
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Ejdebäck, Mikael
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Gray, Pearl
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Jefferies, Caroline
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Wietek, Claudia
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors2003In: Journal of Endotoxin Research, ISSN 0968-0519, E-ISSN 1743-2839, Vol. 9, no 1, p. 55-59Article in journal (Refereed)
    Abstract [en]

    Signal transduction processes activated by Toll-like receptors (TLRs) include the important transcription factor NF-kappaB and 2 MAP kinases, p38 and Jun N-terminal kinase. These signals ultimately give rise to increased expression of a multitude of pro-inflammatory proteins. Receptor-proximal proteins involved in signalling by all TLRs include the adapter MyD88, 3 IRAKs (IRAK-4, IRAK and IRAK-2), Tollip, Traf-6 and TAK-1. Differences between signals generated by TLRs are emerging, with both TLR4 and TLR2 signalling requiring an additional adapter termed MyD88-adapter-like (Mal; also known as TIRAP). MyD88 and Mal both have a homologous Toll/IL-1 receptor (TIR) domain although they differ in their N-termini, with MyD88 possessing a death domain. In addition, structural models reveal marked differences in surface charges which, when taken with surface charge differences between TLR2 and TLR4 TIR domains, may indicate that TLR4 but not TLR2 recruits Mal directly. Another difference is that Mal can become phosphorylated. Future studies on Mal will reveal specificities in signal transduction by different TLRs, which may ultimately provide molecular explanations for specificities in the innate immune response to infection.

  • 19.
    Sigfridsson, Kalle
    et al.
    Department of Biochemistry and Biophysics, Lundberg Laboratory, Göteborg University / Chalmers University of Technology, Göteborg, Sweden.
    Ejdebäck, Mikael
    Department of Biochemistry and Biophysics, Lundberg Laboratory, Göteborg University / Chalmers University of Technology, Göteborg, Sweden.
    Sundahl, Mikael
    Department of Organic Chemistry, Chalmers University of Technology, Göteborg, Sweden.
    Hansson, Örjan
    Department of Biochemistry and Biophysics, Lundberg Laboratory, Göteborg University / Chalmers University of Technology, Göteborg, Sweden.
    Electron transfer in ruthenium-modified spinach plastocyanin mutants1998In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, E-ISSN 1096-0384, Vol. 351, no 2, p. 197-206Article in journal (Refereed)
    Abstract [en]

    Four site-directed mutants of spinach plastocyanin, Pc(Leu12His), Pc(Leu15His), Pc(Thr79His), and Pc(Lys81His), have been modified by covalent attachment of a photoactive [Ru(bpy)2(im)]2+ complex at the surface-exposed histidine residues. The Pc-Ru complexes were characterized with optical absorption, CD, and EPR spectroscopy and their spectra were found to be similar to the unmodified proteins except in the case of the Pc(Leu12His) mutant which lost the Cu ion irreversibly during the Ru modification. Electron transfer (ET) within the other Pc-Ru complexes was studied with time-resolved optical spectroscopy, using an external-quencher approach. The fully reduced [Cu(I), Ru(II)] proteins were photoexcited and subsequently oxidized by an external quencher, [Ru(NH3)6]Cl3, forming the [Cu(I), Ru(III)] proteins. This was followed by an internal ET from Cu(I) to Ru(III). The rates of the internal ET reactions exhibit an exponential dependence on metal-to-metal separation, with a decay factor of 1.1 A-1. From a temperature-dependence study of the Ru-modified Pc(Lys81His) protein, a reorganization energy for the Cu-to-Ru ET reaction of 1.2 eV was determined. In this analysis it was found necessary to include an appreciable temperature dependence in the driving force of the ET reaction.

  • 20.
    Svensson, Maria
    et al.
    University of Skövde, School of Life Sciences.
    Lundh, Dan
    University of Skövde, School of Humanities and Informatics.
    Ejdebäck, Mikael
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Mandal, Abul
    University of Skövde, School of Life Sciences.
    Functional prediction of a T-DNA tagged gene of Arabidopsis thalianaby in silico analysis2004In: Journal of Molecular Modeling, ISSN 1610-2940, E-ISSN 0948-5023, Vol. 10, no 2, p. 130-138Article in journal (Refereed)
    Abstract [en]

    We have employed a gene-knockout approach using T-DNA tagging and in vivo gene fusion in Arabidopsis thaliana for identification and isolation of specific plant genes. Screening of about 3,000 T-DNA tagged lines resulted in identification of a mutant line (no. 197) exhibiting a significant delay in flowering. From this line a 600-bp plant DNA fragment downstream of the left T-DNA junction was cloned by inverse PCR. BLAST searching in the A. thaliana genomic database indicated a putative gene, frf (flowering regulating factor), with unknown function downstream of the T-DNA insert. Bioinformatic tools were used to predict possible protein structure and function. The protein structure predicted by fold recognition indicates that frf is a transcriptional regulator, a ligand-binding receptor responsive to steroids and hormones. Analyzing the predicted results and the phenotype of the T-DNA tagged plant we hypothesized that FRF might be involved in hormone response in A. thaliana. For verification of this hypothesis we exposed the plants of line no. 197 to gibberellic acid (GA3), a potential growth regulator in higher plants. This treatment resulted in an earlier onset of flowering, almost similar to that in wild type control plants.

  • 21.
    Ubbink, Marcellus
    et al.
    Leiden University.
    Ejdebäck, Mikael
    Göteborgs universitet.
    Crowley, Peter B.
    Schlarb, B. G.
    Howe, C. J.
    Karlsson, B. G.
    Bendall, D. S.
    Canters, G. W.
    The transient complex of the redox proteins cytochrome f and plastocyanin studied by NMR1999In: Journal of Inorganic Biochemistry, ISSN 0162-0134, E-ISSN 1873-3344, Vol. 74, no 1-4, p. 321-Article in journal (Other academic)
  • 22.
    Ubbink, Marcellus
    et al.
    Department of Biochemistry and Cambridge Centre for Molecular Recognition, University of Cambridge, England / Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, The Netherlands.
    Ejdebäck, Mikael
    Department of Biochemistry and Biophysics, Göteborg University, Sweden / Chalmers University of Technology, Lundbergslaboratoriet, Göteborg, Sweden.
    Karlsson, B. Göran
    Department of Biochemistry and Biophysics, Göteborg University, Sweden / Chalmers University of Technology, Lundbergslaboratoriet, Göteborg, Sweden.
    Bendall, Derek S.
    Department of Biochemistry and Cambridge Centre for Molecular Recognition, University of Cambridge, England.
    The structure of the complex of plastocyanin and cytochrome f, determined by paramagnetic NMR and restrained rigid-body molecular dynamics1998In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 6, no 3, p. 323-335Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The reduction of plastocyanin by cytochrome f is part of the chain of photosynthetic electron transfer reactions that links photosystems II and I. The reaction is rapid and is influenced by charged residues on both proteins. Previously determined structures show that the plastocyanin copper and cytochrome f haem redox centres are some distance apart from the relevant charged sidechains, and until now it was unclear how a transient electrostatic complex can be formed that brings the redox centres sufficiently close for a rapid reaction.

    RESULTS: A new approach was used to determine the structure of the transient complex between cytochrome f and plastocyanin. Diamagnetic chemical shift changes and intermolecular pseudocontact shifts in the NMR spectrum of plastocyanin were used as input in restrained rigid-body molecular dynamics calculations. An ensemble of ten structures was obtained, in which the root mean square deviation of the plastocyanin position relative to cytochrome f is 1.0 A. Electrostatic interaction is maintained at the same time as the hydrophobic side of plastocyanin makes close contact with the haem area, thus providing a short electron transfer pathway (Fe-Cu distance 10.9 A) via residues Tyr1 or Phe4 (cytochrome f) and the copper ligand His87 (plastocyanin).

    CONCLUSIONS: The combined use of diamagnetic and paramagnetic chemical shift changes makes it possible to obtain detailed information about the structure of a transient complex of redox proteins. The structure suggests that the electrostatic interactions 'guide' the partners into a position that is optimal for electron transfer, and which may be stabilised by short-range interactions.

  • 23.
    Verma, Deepti
    et al.
    Linköping University.
    Eriksson, Per
    Linköping University.
    Sahdo, Berolla
    Örebro University.
    Persson, Alexander
    Linköping University.
    Ejdebäck, Mikael
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Särndahl, Eva
    Örebro University.
    Söderkvist, Peter
    Linköping University.
    Two Adult Siblings with Atypical Cryopyrin Associated Periodic Syndrome (CAPS) due to a Novel M299V Mutation in the NLRP3 Gene.2010In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, no 7, p. 2138-2143Article in journal (Refereed)
    Abstract [en]

    Objective: The NALP3 inflammasome is a multiprotein complex that triggers caspase 1–mediated interleukin-1β (IL-1β) release. Mutations in the gene encoding NALP3 (NLRP3) underlie the cryopyrin-associated periodic syndrome (CAPS). The aim of this study was to report a novel NLRP3 mutation in 2 siblings of Swedish descent in whom symptoms first presented in adulthood.

    Methods: Mutation analysis of NLRP3 was performed on DNA from patients with CAPS and 100 control subjects. For assessment of caspase 1 and IL-1β, blood was collected from patients and age- and sex-matched healthy control subjects. Genetic constructs containing mutant or wild-type NLRP3 were transduced into THP-1 cells, followed by assessment of IL-1β levels in cell supernatant.

    Results: Both siblings carried a novel M299V mutation in NLRP3, which was not present in the control population. The samples obtained from the patients displayed increased caspase 1 activity and elevated IL-1β levels at basal conditions as compared with healthy control subjects. THP-1 cells expressing mutated M299V revealed almost 10-fold higher IL-1β production compared with the wild-type construct.

    Conclusion: M299V is an activating mutation in NLRP3 resulting in elevated spontaneous caspase 1 activity and IL-1β levels. The classic CAPS phenotype was lacking in these adult siblings. Whereas one sibling displayed a milder phenotype that has so far responded satisfactorily to oral nonsteroidal antiinflammatory drugs in combination with low-dose corticosteroids, the inflammatory symptoms in the sibling with the more severe case responded well to IL-1β blockade. Understanding the pathogenic mechanism underlying such disorders can be helpful for the physician. Our study reinforces the importance of genetic testing and laboratory investigations in combination with careful phenotypic evaluation for the diagnosis of such patients.

  • 24. Young, S
    et al.
    Ejdebäck, Mikael
    Göteborgs universitet.
    Sigfridsson, K
    Samuelson, A
    Hansson, Örjan
    Spectroscopic and kinetic characterization of site-specific mutants of plastocyanin1995In: Photosynthesis: From Light To Biosphere, Vol. 2 / [ed] Mathis, P., Dordrecht: Kluwer Academic Publishers, 1995, p. 669-672Conference paper (Other academic)
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