HLA-B27 lacking associated beta2-microglobulin rearranges to auto-display or cross-display residues 169-181: a novel molecular mechanism for spondyloarthropathies

FEBS Letters
Manni Luthra-Guptasarma, Balvinder Singh

Abstract

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.

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Citations

Oct 28, 2008·Rheumatology International·Zhen WuJieruo Gu
Jun 16, 2005·Current Opinion in Rheumatology·Tae-Hwan KimRobert D Inman
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Apr 12, 2015·Annual Review of Immunology·Paul Bowness
Oct 30, 2016·International Journal of Biological Macromolecules·Manish Kumar Rana, Manni Luthra-Guptasarma
Mar 29, 2019·Clinical Rheumatology·Kaitlyn M HayesJanet E Pope
Oct 14, 2005·The Journal of Biological Chemistry·Christine RückertBarbara Uchanska-Ziegler
Mar 6, 2017·Molecular Medicine Reports·Bin ChenWeidong Xu

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