Enthalpy driven temperature-sensitive conformational changes in a metamorphic protein involved in the cyanobacterial circadian clock.

Metamorphic proteins switch reversibly between distinctly different folds often with different functions under physiological conditions. Here, the kinetics and thermodynamics of the fold-switching at different temperatures in a metamorphic protein, KaiB, involved in cyanobacterial circadian clock, reveal that enthalpy-driven the fold-switching to form fold-switched KaiB (fsKaiB) and the fsKaiB and ground-state KaiB (gsKaiB) are more dominantly at lower and higher temperatures, respectively. Thermodynamic analysis indicates that conformational and solvent entropy have opposing effects on KaiB's fold-switching. The folding kinetic reveals that as KaiB folds, it preferentially folds into gsKaiB and then switches fold to fsKaiB. Temperature-sensitive protein fold-switching can be further extended into applications, such as new temperature-sensitive molecular switcher and biosensors development.