Slow unfolded-state structuring in Acyl-CoA binding protein folding revealed by simulation and experiment.

ABSTRACT: Protein folding is a fundamental process in biology, key to understanding many human diseases. Experimentally, proteins often appear to fold via simple two- or three-state mechanisms involving mainly native-state interactions, yet recent network models built from atomistic simulations of small proteins suggest the existence of many possible metastable states and folding pathways. We reconcile these two pictures in a combined experimental and simulation study of acyl-coenzyme A binding protein (ACBP), a two-state folder (folding time ~10 ms) exhibiting residual unfolded-state structure, and a putative early folding intermediate. Using single-molecule FRET in conjunction with side-chain mutagenesis, we first demonstrate that the denatured state of ACBP at near-zero denaturant is unusually co

SUBMITTER: Voelz VA 

PROVIDER: S-EPMC3462454 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature