Bound Peptide-Dependent Thermal Stability of Major Histocompatibility Complex Class II Molecule I-Ek

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• 作者：Keigo Saito ; Masayuki Oda ; Akinori Sarai ; Takachika Azuma ; and Haruo Kozono
• 刊名：Biochemistry
• 出版年：2004
• 出版时间：August 10, 2004
• 年：2004
• 卷：43
• 期：31
• 页码：10186 - 10191
• 全文大小：99K
• 年卷期：v.43,no.31(August 10, 2004)
• ISSN：1520-4995

文摘

We used differential scanning calorimetry to study the thermal denaturation of murine majorhistocompatibility complex class II, I-E^k, accommodating hemoglobin (Hb) peptide mutants possessing asingle amino acid substitution of the chemically conserved amino acids buried in the I-E^k pocket (positions71 and 73) and exposed to the solvent (position 72). All of the I-E^k-Hb(mut) molecules exhibited greaterthermal stability at pH 5.5 than at pH 7.4, as for the I-E^k-Hb(wt) molecule, which can explain the peptideexchange function of MHC II. The thermal stability was strongly dependent on the bound peptide sequences;the I-E^k-Hb(mut) molecules were less stable than the I-E^k-Hb(wt) molecules, in good correlation with therelative affinity of each peptide for I-E^k. This supports the notion that the bound peptide is part of thecompletely folded MHC II molecule. The thermodynamic parameters for I-E^k-Hb(mut) folding can explainthe thermodynamic origin of the stability difference, in correlation with the crystal structural analysis,and the limited contributions of the residues to the overall conformation of the I-E^k-peptide complex.We found a linear relationship between the denaturation temperature and the calorimetric enthalpy change.Thus, although the MHC II-peptide complex could have a diverse thermal stability spectrum, dependingon the amino acid sequences of the bound peptides, the conformational perturbations are limited. Thevariations in the MHC II-peptide complex stability would function in antigen recognition by the T cellreceptor by affecting the stability of the MHC II-peptide-T cell receptor ternary complex.