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Inflammatory processes are accompanied by the post-translational modifi-cation of certain arginine residues to yield citrulline, and a pH decrease in the affected tissue, which might influence the protonation of histidine resi-dues within proteins. | IFEBS Journal Influence of inflammation-related changes on conformational characteristics of HLA-B27 subtypes as detected by IR spectroscopy Heinz Fabian1 Bernhard Loll2 Hans Huser3 Dieter Naumann1 Barbara Uchanska-Ziegler3 and Andreas Ziegler3 1 Robert Koch-Institut Berlin Germany 2 Institut fur Chemie und Biochemie Abteilung Strukturbiochemie Freie Universitat Berlin Germany 3 Institut fur Immungenetik Charite-Universitatsmedizin Berlin Freie Universitat Berlin Germany Keywords ankylosing spondylitis citrullination conformationaldifferences HLA-B27 subtypes IR spectroscopy Correspondence D. Naumann Robert Koch-Institut P 25 Nordufer 20 D-13353 Berlin Germany Fax 49 30 1875 42606 Tel 49 30 1875 42259 E-mail naumannd@rki.de Received 3 December 2010 revised 8 March 2011 accepted 11 March 2011 doi 10.1111 j.1742-4658.2011.08097.x Inflammatory processes are accompanied by the post-translational modification of certain arginine residues to yield citrulline and a pH decrease in the affected tissue which might influence the protonation of histidine residues within proteins. We employed isotope-edited IR spectroscopy to investigate whether conformational features of two human major histocompatibility antigen class I subtypes HLA-B 2705 and HLA-B 2709 are affected by these changes. Both differ only in residue 116 Asp vs. His within the peptide-binding grooves but are differentially associated with inflammatory rheumatic disorders. Our analyses of the two HLA-B27 subtypes in complex with a modified self-peptide containing a citrulline RRKWURWHL U citrulline revealed that the heavy chain is more flexible in the HLA-B 2705 subtype than in the HLA-B 2709 subtype. Together with our previous studies of HLA-B27 subtypes complexed with the unmodified self-peptide RRKWRRWHL these findings support the existence of subtype-specific conformational features of the heavy chains under physiological conditions which are undetectable by X-ray crystallography and exist irrespective of the .
