title: Dynamic characteristics of a peptide-binding groove of human HLA-A2 class I MHC molecules: normal mode analysis of the antigen peptide-class I MHC complex.
abstract: Class I major histocompatibility complex (MHC) binds antigen peptides with various sequences. We performed a normal mode analysis of HLA-A2 MHC that binds three peptides with different affinity. HLA-A2 MHC has a peptide-binding groove composed of two alpha-helices (residue 49-84, residue 140-179). Some residues in the center of the groove showed an increase in fluctuations and some residue pairs between two helix groups showed a negative change in correlations by removing the antigen peptide. The extent of the fluctuation and correlation changes correlated well with the experimental ranking of the three peptides in binding affinity. Some definite anti-correlative motions were found between two helix groups in low frequency modes (<50 cm(-1)) by removing the antigen peptide. We propose that the above anti-correlative motions play an important role to bind the antigen peptide, especially in obtaining a "dynamic fit."
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nojima
authors.forename: Mayuko
authors.initials: M
authors.lastname: Takeda-Shitaka
authors.forename: Youji
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Masaaki
authors.initials: M
authors.lastname: Adachi
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Yoneda
authors.forename: Kenshu
authors.initials: K
authors.lastname: Kamiya
authors.forename: Hideaki
authors.initials: H
authors.lastname: Umeyama
mesh_terms: D018360:Crystallography, X-Ray; D004563:Electrochemistry; D005805:Genes, MHC Class I / Q000235:genetics*; D015789:HLA-A2 Antigen / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D015789:HLA-A2 Antigen; D010455:Peptides