Narzi D, Becker C, Fiorillo MT, Uchanska-Ziegler B, Ziegler A, Böckmann R (2012)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2012
Book Volume: 415
Pages Range: 429-42
Volume: 415
Issue: 2
Journal Issue: 2
DOI: 10.1016/j.jmb.2011.11.021
Major histocompatibility complex (MHC) class I proteins are expressed on the cell surface where they present foreign and self-peptides to effector cells of the immune system. While an understanding of the structural prerequisites for antigen presentation has already been achieved, insight into subtype- or peptide-dependent dynamical characteristics of a peptide-MHC antigen is so far largely obscure. We approached this problem by employing 400-ns molecular dynamics simulations with two human MHC class I subtypes as model systems: the ankylosing spondylitis-associated HLA-B∗27:05 and the non-ankylosing spondylitis-associated HLA-B∗27:09. Both proteins differ only by a micropolymorphism at the floor of the peptide binding groove (Asp116His). A viral (pLMP2) and three self-peptides (pVIPR, pGR, and TIS) were evaluated. The stability of the binding grooves was found to be both subtype dependent and peptide dependent. A detachment from the C- and/or N-terminal pockets was observed for all peptides except TIS, resulting in a stabilization of the α1-helix in both TIS-displaying subtypes. Estimates of the entropy associated with the bound peptides showed an increased entropy for pLMP2 presented by B∗27:05 as compared to B∗27:09, in contrast to the self-peptides. Additionally, the flexibility of the α1-helix that is probably important for receptor binding to the B27:peptide epitope is significantly enhanced for B∗27:05. These in silico results show that the dynamic properties of peptide-MHC complexes are affected both by the bound peptide and by micropolymorphisms of the heavy chain. Our findings suggest a role for the conformational flexibility of MHC class I molecules in the context of recognition by receptors on effector cells.
APA:
Narzi, D., Becker, C., Fiorillo, M.T., Uchanska-Ziegler, B., Ziegler, A., & Böckmann, R. (2012). Dynamical characterization of two differentially disease associated MHC class I proteins in complex with viral and self-peptides. Journal of Molecular Biology, 415(2), 429-42. https://doi.org/10.1016/j.jmb.2011.11.021
MLA:
Narzi, Daniele, et al. "Dynamical characterization of two differentially disease associated MHC class I proteins in complex with viral and self-peptides." Journal of Molecular Biology 415.2 (2012): 429-42.
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