A protein-folding reaction under kinetic control

TitleA protein-folding reaction under kinetic control
Publication TypeJournal Article
Year of Publication1992
AuthorsBaker, D., Sohl J. L., & Agard D. A.
JournalNature
Volume356
Issue6366
Pagination263-5
Date Published1992 Mar 19
ISSN0028-0836
KeywordsChemistry, Physical, Circular Dichroism, Guanidine, Guanidines, Kinetics, Physicochemical Phenomena, Primary Publication, Protein Conformation, Protein Denaturation, Protein Precursors, Serine Endopeptidases
Abstract

Synthesis of alpha-lytic protease is as a precursor containing a 166 amino-acid pro region transiently required for the correct folding of the protease domain. By omitting the pro region in an in vitro refolding reaction we trapped an inactive, but folding competent state (I) having an expanded radius yet native-like secondary structure. The I state is stable for weeks at physiological pH in the absence of denaturant, but rapidly folds to the active, native state on addition of the pro region as a separate polypeptide chain. The mechanism of action of the pro region is distinct from that of the chaperonins: rather than reducing the rate of off-pathway reactions, the pro region accelerates the rate-limiting step on the folding pathway by more than 10(7). Because both the I and native states are stable under identical conditions with no detectable interconversion, the folding of alpha-lytic protease must be under kinetic and not thermodynamic control.

Alternate JournalNature
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