TY - JOUR
T1 - Folding pathway mediated by an intramolecular chaperone
AU - Shinde, Ujwal
AU - Li, Yuyun
AU - Chatterjee, Sukalyan
AU - Inouye, Masayori
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1993/8/1
Y1 - 1993/8/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8346198
AN - SCOPUS:0027219717
SN - 0027-8424
VL - 90
SP - 6924
EP - 6928
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -