Mapping the FF domain folding pathway via structures of transiently populated folding intermediates.

ABSTRACT: Despite the tremendous accomplishments of AlpaFold2/3 in predicting biomolecular structure, the protein folding problem remains unsolved in the sense that accurate atomistic models of how protein molecules fold into their native conformations from an unfolded ensemble are still elusive. Here, using chemical exchange saturation transfer (CEST) NMR experiments and a comprehensive four-state kinetic model of the folding trajectory of a 71 residue four-helix bundle FF domain from human HYPA/FBP11 we present an atomic resolution structure of a transiently formed intermediate, I2, that along with the structure of a second intermediate, I1, provides a description of the FF domain folding trajectory. By recording CEST profiles as a function of urea concentration the extent of compaction along the

SUBMITTER: De D 

PROVIDER: S-EPMC11648910 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature