title: 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.
abstract: Major histocompatibility complexes (MHCs) mainly fall into class I and class II. The two classes have similar structures, with two membrane-proximal immunoglobulin-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 II 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 II and class I. Both membrane-proximal domains (the alpha2 and beta2 domains) of class II MHC, especially the alpha2 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 alpha2 domain neighborhood. By contrast, the two membrane-proximal domains (the alpha3 and beta2m 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.
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nojima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kanou
authors.forename: Kenshu
authors.initials: K
authors.lastname: Kamiya
authors.forename: Koichiro
authors.initials: K
authors.lastname: Atsuda
authors.forename: Hideaki
authors.initials: H
authors.lastname: Umeyama
authors.forename: Mayuko
authors.initials: M
authors.lastname: Takeda-Shitaka
mesh_terms: D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000276:immunology; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D010455:Peptides