Differential peptide dynamics is linked to major histocompatibility complex polymorphism.
Böckmann R, Grubmüller H (2004)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2004
Journal
Publisher: American Society for Biochemistry and Molecular Biology
Book Volume: 279
Pages Range: 28197-201
Volume: 279
Issue: 27
Journal Issue: 27
Abstract
Peptide presentation by major histocompatibility complex (MHC) molecules is of central importance for immune responses, which are triggered through recognition of peptide-loaded MHC molecules (pMHC) by cellular ligands such as T-cell receptors (TCR). However, a unifying link between structural features of pMHC and cellular responses has not been established. Instead, pMHC/TCR binding studies suggest conformational and/or flexibility changes of the binding partners as a possible cause of differential T-cell stimulation, but information on real-time dynamics is lacking. We therefore probed the real-time dynamics of a MHC-bound nonapeptide (m9), by combining time-resolved fluorescence depolarization and molecular dynamics simulations. Here we show that the nanosecond dynamics of this peptide presented by two human MHC class I subtypes (HLA-B*2705 and HLA-B*2709) with differential autoimmune disease association varies dramatically, despite virtually identical crystal structures. The peptide dynamics is linked to the single, buried polymorphic residue 116 in the peptide binding groove. Pronounced peptide flexibility is seen only for the non-disease-associated subtype HLA-B*2709, suggesting an entropic control of peptide recognition. Thermodynamic data obtained for two additional peptides support this hypothesis.
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Germany (DE)How to cite
APA:
Böckmann, R., & Grubmüller, H. (2004). Differential peptide dynamics is linked to major histocompatibility complex polymorphism. Journal of Biological Chemistry, 279(27), 28197-201. https://doi.org/10.1074/jbc.C400128200
MLA:
Böckmann, Rainer, and Helmut Grubmüller. "Differential peptide dynamics is linked to major histocompatibility complex polymorphism." Journal of Biological Chemistry 279.27 (2004): 28197-201.
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