Dynamic Influence of the Two Membrane-Proximal Immunoglobulin-Like Domains upon the Peptide-Binding Platform Domain in Class I and Class II Major Histocompatibility Complexes: Normal Mode Analysis

Major histocompatibility complexes (MECs) mainly fall into class I and class II. The two classes have similar structures, with two membrane-proximal immunogloublin-like domains and a peptide-binding platform domain, though their organizations are different. We simulated the dynamics of a whole and partial model deficient in either of the two membrane-proximal domains for class I and class 11 using normal mode analysis. Our study showed that the influence of the two membrane-proximal domains upon the dynamics of the platform domain were decisively different between class 11 and class I. Both membrane-proximal domains (the alpha 2 and beta 2 domains) of class 11 MHC. especially the alpha 2 domain, influenced the most important pocket that accommodates a large hydrophobic anchor side chain of the N-terminal side of the bound peptide, though the pocket was not in the alpha 2 domain neighborhood. By contrast, the two membrane-proximal domains (the alpha 3 and beta(2)m domains) of class I MHC had little influence upon the most important pocket that accommodates the N-terminal residue of the bound peptide. These results suggest that the two membrane-proximal domains of class II MHC have a greater influence upon peptide-binding than those of class I MHC.