title: Energetic asymmetry among hydrogen bonds in MHC class II*peptide complexes.
abstract: Comparison of crystallized MHC class II*peptide complexes has revealed that, in addition to pocket interactions involving the peptide side chains, peptide binding to MHC class II molecules is characterized by a series of hydrogen bonds between genetically conserved amino acid residues in the class II molecule and the main chain of the peptide. Many class II*peptide structures have two sets of symmetrical hydrogen bonds at the opposite ends of the class II antigen-binding groove (beta-His-81, beta-Asn-82 vs. alpha-His-68, alpha-Asn-69). In this study, we alter these peripheral hydrogen bonds and measure the apparent contribution of each to the kinetic stability of peptide* II complexes. Single conservative amino substitutions were made in the I-A(d) protein to eliminate participation as a hydrogen bonding residue, and the kinetic stability of a diverse set of peptides bound to the substituted I-A(d) proteins was measured. Although each hydrogen bond does contribute to peptide binding, our results point to the striking conclusion that those hydrogen bonds localized to the amino terminus of the peptide contribute profoundly and disproportionately to the stability of peptide interactions with I-A(d). We suggest that the peripheral hydrogen bonds at the amino terminus of the bound peptide that are conserved in all class II*peptide crystal structures solved thus far form a cooperative network that critically regulates peptide dissociation from the class II molecule.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: McFarland
authors.forename: J F
authors.initials: JF
authors.lastname: Katz
authors.forename: C
authors.initials: C
authors.lastname: Beeson
authors.forename: A J
authors.initials: AJ
authors.lastname: Sant
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*
chemical_list: D000949:Histocompatibility Antigens Class II; D010455:Peptides