Folding pathway mediated by an intramolecular chaperone

U. Shinde, Y. Li, S. Chatterjee, M. Inouye

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82 Scopus citations

Abstract

The N-terminal propeptide of subtilisin, a serine protease, functions as an intramolecular chaperone which is crucial for proper folding of the active enzyme. This nascent N-terminal propeptide is removed after completion of the folding process. Here we present a possible pathway by which intramolecular chaperones mediate protein folding. Using circular dichroism to analyze acid- denatured subtilisin we have identified a folding-competent state which can refold to an active conformation in the absence of the propeptide. Earlier work had shown that guanidine hydrochloride-denatured subtilisin was in a state incapable of folding in absence of its propeptide. Comparison of the folding-incompetent and folding-competent states indicates that refolding is facilitated by the presence of residual structure present only in the folding-competent state. The analysis further indicates that the propeptide is essential for inducing this state. Therefore the folding-competent state may lie on-or be in rapid equilibrium with an intermediate on-the folding pathway of subtilisin. In the absence of the propeptide, formation of such a state-and hence refolding-is extremely slow.

Original languageEnglish (US)
Pages (from-to)6924-6928
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number15
DOIs
StatePublished - Jan 1 1993

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