title: Contribution of a single hydrogen bond between betaHis81 of MHC class II I-E(k) and the bound peptide to the pH-dependent thermal stability.
abstract: To determine the energetic contribution of the hydrogen bond between betaHis81 of the major histocompatibility complex class II (MHC II) molecule, I-E(k), and the bound hemoglobin peptide (Hb), we analyzed the thermal stability of the hydrogen bond-disrupted mutant, I-E(k)-Hb betaH81Y, in which the betaHis81 residue was replaced with Tyr, by differential scanning calorimetry. The thermal stability of the I-E(k)-Hb betaH81Y mutant was lower than that of the I-E(k)-Hb wild-type, mainly due to the decreased enthalpy change. The difference in the denaturation temperature of the I-E(k)-Hb betaH81Y mutant as compared with that of the I-E(k)-Hb wild-type at pH 5.5 was only slightly smaller than that at pH 7.4, in agreement with the increased stability at an acidic pH, a unique characteristic of MHC II. Thus, the hydrogen bond contributed by betaHis81 is critical for peptide binding, and is independent of pH, which can alter the hydrophilicity of the His residue.
authors.affiliation: Research Institute for Biological Sciences (RIBS), Tokyo University of Science.
authors.forename: Keigo
authors.initials: K
authors.lastname: Saito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Oda
authors.forename: Akinori
authors.initials: A
authors.lastname: Sarai
authors.forename: Takachika
authors.initials: T
authors.lastname: Azuma
authors.forename: Haruo
authors.initials: H
authors.lastname: Kozono
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D006454:Hemoglobins / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D013696:Temperature; D013816:Thermodynamics; D014443:Tyrosine / Q000737:chemistry
chemical_list: D006454:Hemoglobins; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010446:Peptide Fragments; D014443:Tyrosine; D006639:Histidine