Ankylosing Spondylitis Research Today is a free monthly online journal that collates and summarizes the latest research about Ankylosing Spondylitis, including details on diagnosis, treatment, symptoms, causes.

HLA-B27 subtypes differentially associated with disease exhibit conformational differences in solution.

Fabian H, Huser H, Narzi D, Misselwitz R, Loll B, Ziegler A, Böckmann RA, Uchanska-Ziegler B, Naumann D

Robert Koch-Institut, P 25, Nordufer 20, D-13353 Berlin, Germany. fabianh@rki.de

Human leukocyte antigen (HLA) class I molecules consist of a heavy chain, beta(2)-microglobulin, and a peptide that are noncovalently bound. Certain HLA-B27 subtypes are associated with ankylosing spondylitis (such as HLA-B*2705), whereas others (such as HLA-B*2709) are not. Both differ in only one residue (Asp116 and His116, respectively) in the F pocket that accommodates the peptide C-terminus. An isotope-edited IR spectroscopy study of these HLA-B27 subtypes complexed with the self-peptide RRKWRRWHL was carried out, revealing that the heavy chain is more flexible in the HLA-B*2705 than in the HLA-B*2709 subtype. In agreement with these experimental data, molecular dynamics simulations showed an increased flexibility of the HLA-B*2705 binding groove in comparison with that of the HLA-B*2709 subtype. This difference correlates with an opening of the HLA-B*2705 binding groove, accompanied by a partial detachment of the C-terminal peptide anchor. These combined results demonstrate how the deeply embedded polymorphic heavy-chain residue 116 influences the flexibility of the peptide binding groove in a subtype-dependent manner, a feature that could also influence the recognition of the HLA-B27 complexes by effector cells.

Published 5 February 2008 in J Mol Biol, 376(3): 798-810.
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