Fold-switching proteins respond to cellular stimuli by remodeling their secondary structures and changing their functions. Whereas several previous reviews have focused on various structural, physical-chemical, and evolutionary aspects of this newly emerging class of proteins, this minireview focuses on how fold switching modulates protein function and regulates biological processes. It first compares and contrasts fold switchers with other known types of proteins. Second, it presents examples of how various proteins can change their functions through fold switching. Third, it demonstrates that fold switchers can regulate biological processes by discussing two proteins, RfaH and KaiB, whose dramatic secondary structure remodeling events directly affect gene expression and a circadian clock, respectively. Finally, this minireview discusses how the field of protein fold switching might advance.
