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Influence of inflammation‐related changes on conformational characteristics of HLA‐B27 subtypes as detected by IR spectroscopy
Author(s) -
Fabian Heinz,
Loll Bernhard,
Huser Hans,
Naumann Dieter,
UchanskaZiegler Barbara,
Ziegler Andreas
Publication year - 2011
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08097.x
Subject(s) - peptide , citrulline , chemistry , arginine , human leukocyte antigen , hla b27 , major histocompatibility complex , citrullination , histidine , biochemistry , protonation , peptide sequence , protein structure , biophysics , antigen , biology , amino acid , immunology , gene , ion , organic chemistry
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 sequence of the bound peptide and its binding mode. They might thus influence antigenic properties of the respective HLA‐B27 subtype. Furthermore, a decrease in the pH from 7.5 to 5.6 during the analyses had an influence only on HLA‐B*2709 complexed with the unmodified self‐peptide, where His116 is not contacted by any peptide side chain. This permits us to conclude that histidines, and in particular His116, influence the stability of MHC:peptide complexes. The conditions prevailing in inflammatory environments in vivo might thus also exert an impact on selected conformational features of HLA‐B27:peptide complexes. Structured digital abstract• B*27 and VIPR bind by biophysical ( View interaction ).