%0 Journal Article
%@ 0014-5793
%A Luthra-Guptasarma, Manni
%A Singh, Balvinder
%D 2004
%F open:970
%I Elsevier Science
%J FEBS letters
%K HLA-B27; Ankylosing spondylitis; Protein misfolding; Detailed molecular mechanism; MHC auto display; Autoimmune disorders
%N 1-3
%P 1-8
%T HLA-B27 lacking associated beta2-microglobulin rearranges to auto-display or cross-display residues 169-181: a novel molecular mechanism for spondyloarthropathies.
%U http://crdd.osdd.net/open/970/
%V 575
%X Expression of the MHC class I allele, HLA-B27, is correlated with autoimmune disease. The misfolding and association of B27 heavy chains through non-native disulfide bonds has recently been implicated. Here, we propose that beta2m-free, peptide-free heavy chains support a helix-coil transition in the segment leading from the alpha2 domain to the alpha3 domain, facilitating rotation of backbone angles around residues 167/168, and allowing residues 169-181 (identical to a known B27 ligand) to loop around and occupy the molecule's own peptide-binding cleft. Such 'auto-display', occurring either within B27 molecules, or between B27 molecules, could provoke autoimmune attack.
%Z Copyright of this article belongs to Elsevier Science.