title: A role for the P1 anchor residue in the thermal stability of MHC class II molecule I-Ab.
abstract: The thermal stability of the murine MHC class II molecule, I-A(b), in complex with invariant chain-derived peptide (CLIP) and an antigenic peptide derived from the alpha subunit of the I-E molecule (Ealpha) at mildly acidic and neutral pH were analyzed using circular dichroism (CD). The stability of I-A(b)-CLIP was increased by a single amino acid substitution in the P1 anchor residue, from Met of CLIP to Phe of Ealpha, similar, in this respect, to I-A(b)-Ealpha. This indicates that hydrophobic interaction in the P1 pocket is critical and plays a primary role in the stability of the complex. The structural models of I-A(b)-peptides based on the crystal structure of I-A(d) might explain the increased stability and the preference for hydrophobic residues in this site. Taken together with what is known of the resident stability at a mildly acidic pH, the difference in stability would closely correlate with the ability of MHC class II to exchange peptides from CLIP to antigenic peptides in the endosome.
authors.affiliation: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, 278-0022, Chiba, Japan.
authors.forename: Toranosuke
authors.initials: T
authors.lastname: Tobita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Oda
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Morii
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuroda
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yoshino
authors.forename: Takachika
authors.initials: T
authors.lastname: Azuma
authors.forename: Haruo
authors.initials: H
authors.lastname: Kozono
mesh_terms: D000818:Animals; D001665:Binding Sites; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; C024138:I-E-antigen; D010446:Peptide Fragments