Fragile protein folds: Sequence and environmental factors affecting the equilibrium of two interconverting, stably folded protein conformations.

ABSTRACT: Recent research on fold-switching metamorphic proteins has revealed some notable exceptions to Anfinsen's hypothesis of protein folding. We have previously described how a single point mutation can enable a well-folded protein domain, one of the two PAS (Per-ARNT-Sim) domains of the human ARNT (aryl hydrocarbon receptor nuclear translocator) protein, to interconvert between two conformers related by a slip of an internal β-strand. Using this protein as a test case, we advance the concept of a "fragile fold," a protein fold that can reversibly rearrange into another fold that differs by a substantial number of hydrogen bonds, entailing reorganization of single secondary structure elements to more drastic changes seen in metamorphic proteins. Here we use a battery of biophysical tests to exa

SUBMITTER: Xu X 

PROVIDER: S-EPMC9119131 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature