Folding pathway mediated by an intramolecular chaperone

Ujwal Shinde, Yuyun Li, Sukalyan Chatterjee, Masayori Inouye

Research output: Contribution to journalArticle

81 Citations (Scopus)

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
StatePublished - Aug 1 1993
Externally publishedYes

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Subtilisin
Protein Folding
Guanidine
Serine Proteases
Circular Dichroism
Acids
Enzymes

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Folding pathway mediated by an intramolecular chaperone. / Shinde, Ujwal; Li, Yuyun; Chatterjee, Sukalyan; Inouye, Masayori.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 15, 01.08.1993, p. 6924-6928.

Research output: Contribution to journalArticle

Shinde, Ujwal ; Li, Yuyun ; Chatterjee, Sukalyan ; Inouye, Masayori. / Folding pathway mediated by an intramolecular chaperone. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 15. pp. 6924-6928.
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