Bound peptide-dependent thermal stability of major histocompatibility complex class II molecule I-Ek.
Biochemistry
; 43(31): 10186-91, 2004 Aug 10.
Article
in En
| MEDLINE
| ID: mdl-15287746
ABSTRACT
We used differential scanning calorimetry to study the thermal denaturation of murine major histocompatibility complex class II, I-E(k), accommodating hemoglobin (Hb) peptide mutants possessing a single amino acid substitution of the chemically conserved amino acids buried in the I-Ek pocket (positions 71 and 73) and exposed to the solvent (position 72). All of the I-Ek-Hb(mut) molecules exhibited greater thermal stability at pH 5.5 than at pH 7.4, as for the I-Ek-Hb(wt) molecule, which can explain the peptide exchange function of MHC II. The thermal stability was strongly dependent on the bound peptide sequences; the I-Ek-Hb(mut) molecules were less stable than the I-Ek-Hb(wt) molecules, in good correlation with the relative affinity of each peptide for I-Ek. This supports the notion that the bound peptide is part of the completely folded MHC II molecule. The thermodynamic parameters for I-Ek-Hb(mut) folding can explain the 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-Ek-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, depending on the amino acid sequences of the bound peptides, the conformational perturbations are limited. The variations in the MHC II-peptide complex stability would function in antigen recognition by the T cell receptor by affecting the stability of the MHC II-peptide-T cell receptor ternary complex.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Thermodynamics
/
Histocompatibility Antigens Class II
Limits:
Animals
Language:
En
Journal:
Biochemistry
Year:
2004
Document type:
Article
Affiliation country:
Japón