Structural principles that govern the peptide-binding motifs of class I MHC molecules.
The peptides that bind class I MHC molecules are restricted in length and often contain key amino acids, anchor residues, at particular positions. The side-chains of peptide anchor residues interact with the polymorphic complementary pockets in MHC peptide-binding grooves and provide the molecular basis for allele-specific recognition of antigenic peptides. We establish correlations between class I MHC specificities for anchor residues and class I MHC sequence markers that occur at the polymorphic positions lining the structural pockets. By analyzing the pocket structures of nine crystallized class I MHC molecules and the modeled structures of another 39 class I MHC molecules, we show that class I pockets can be classified into families that are distinguishable by their common physico-chemical properties and peptide side-chain selectivities. The identification of recurrent structural principles among class I pockets makes it possible to greatly expand the repertoire of known peptide-binding motifs of class I MHC molecules. The evolutionary strategies underlying the emergence of pocket families is briefly discussed.
Department of Biomedical Engineering, Boston University College of Engineering, Boston, MA, 02215, USA.
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Zhang
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Anderson
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DeLisi
D000483:Alleles; D000596:Amino Acids / Q000737:chemistry; D001665:Binding Sites / Q000502:physiology; D019992:Databases as Topic; D019143:Evolution, Molecular; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding / Q000502:physiology; D016415:Sequence Alignment; D055672:Static Electricity
D000596:Amino Acids; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides