Limited internal friction in the rate-limiting step of a two-state protein folding reaction

TitleLimited internal friction in the rate-limiting step of a two-state protein folding reaction
Publication TypeJournal Article
Year of Publication1998
AuthorsPlaxco, K. W., & Baker D.
JournalProceedings of the National Academy of Sciences of the United States of America
Date Published1998 Nov 10
KeywordsBacterial Proteins, Escherichia coli, Models, Molecular, Primary Publication, Protein Conformation, Protein Folding, Recombinant Proteins

Small, single-domain proteins typically fold via a compact transition-state ensemble in a process well fitted by a simple, two-state model. To characterize the rate-limiting conformational changes that underlie two-state folding, we have investigated experimentally the effects of changing solvent viscosity on the refolding of the IgG binding domain of protein L. In conjunction with numerical simulations, our results indicate that the rate-limiting conformational changes of the folding of this domain are strongly coupled to solvent viscosity and lack any significant "internal friction" arising from intrachain collisions. When compared with the previously determined solvent viscosity dependencies of other, more restricted conformational changes, our results suggest that the rate-limiting folding transition involves conformational fluctuations that displace considerable amounts of solvent. Reconciling evidence that the folding transition state ensemble is comprised of highly collapsed species with these and similar, previously reported results should provide a significant constraint for theoretical models of the folding process.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
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