Thermodynamic analysis of the increased stability of major histocompatibility complex class II molecule I-Ek complexed with an antigenic peptide at an acidic pH.
The differential scanning calorimetry analysis of the murine major histocompatibility complex class II molecule, I-E(k), in complex with an antigenic peptide derived from mouse hemoglobin, showed that the thermal stability at the mildly acidic pH is higher than that at the neutral pH. Although the thermal unfolding of I-E(k)-hemoglobin was irreversible, we extracted the equilibrium thermodynamic parameters from the kinetically controlled heat capacity curves. Both the denaturation temperatures and the enthalpy changes were almost independent of the heating rate over 1 degrees C per min. The linear relation between the denaturation temperature and the calorimetric enthalpy change provided the heat capacity changes, which are classified into one for the mildly acidic pH region and another for the neutral pH region. The equilibrium thermodynamic parameters showed that the increased stability at the mildly acidic pH is because of the entropic effect. These thermodynamic data provided new insight into the current structural model of a transition to an open conformation at the mildly acidic pH, which is critical for the peptide exchange function of major histocompatibility complex class II in the endosome.
Saito
Keigo
K
Research Institute for Biological Sciences (RIBS), Tokyo University of Science, 2669, Yamazaki, Noda, Chiba 278-0022, Japan.
Sarai
Akinori
A
Oda
Masayuki
M
Azuma
Takachika
T
Kozono
Haruo
H
D000143:Acids / Q000494:pharmacology; D000818:Animals; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D051379:Mice; D011489:Protein Denaturation; D013696:Temperature; D013816:Thermodynamics
D000143:Acids; D000936:Antigen-Antibody Complex; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen