HLA-B27 subtypes differentially associated with disease exhibit conformational differences in solution.
Febian H, Huser H, Narzi D, Misselwitz R, Loll B, Ziegler A, Böckmann R, Uchanska-Ziegler B, Naumann D (2008)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2008
Journal
Book Volume: 376
Pages Range: 798-810
Volume: 376
Issue: 3
Journal Issue: 3
DOI: 10.1016/j.jmb.2007.12.009
Abstract
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.
Authors with CRIS profile
Daniele Narzi
Professur für Computational Biology
Rainer Böckmann
Professur für Computational Biology
Involved external institutions
Robert Koch-Institut (RKI)
Germany (DE)
Freie Universität Berlin
Germany (DE)
Max-Planck-Institut für medizinische Forschung / Max Planck Institute for Medical Research
Germany (DE)
Germany (DE)
Freie Universität Berlin
Germany (DE)
Max-Planck-Institut für medizinische Forschung / Max Planck Institute for Medical Research
Germany (DE)
How to cite
APA:
Febian, H., Huser, H., Narzi, D., Misselwitz, R., Loll, B., Ziegler, A.,... Naumann, D. (2008). HLA-B27 subtypes differentially associated with disease exhibit conformational differences in solution. Journal of Molecular Biology, 376(3), 798-810. https://doi.org/10.1016/j.jmb.2007.12.009
MLA:
Febian, Heinz, et al. "HLA-B27 subtypes differentially associated with disease exhibit conformational differences in solution." Journal of Molecular Biology 376.3 (2008): 798-810.
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