GroEL and CCT are catalytic unfoldases mediating out-of-cage polypeptide refolding without ATP

Priya S.; Sharma S.K.; Sood V.Mattoo R.U.H.Finka A.Azem A.De Los Rios P.Goloubinoff P.

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GroEL and CCT are catalytic unfoldases mediating out-of-cage polypeptide refolding without ATP

机译：GroEL and CCT are catalytic unfoldases mediating out-of-cage polypeptide refolding without ATP

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Chaperonins are cage-like complexes in which nonnative polypeptides prone to aggregation are thought to reach their native state optimally. However, they also may use ATP to unfold stably bound misfolded polypeptides andmediate the out-of-cage native refolding of large proteins. Here, we show that even without ATP and GroES, bothGroEL andthe eukaryotic chaperonin containingt-complex polypeptide 1 (CCT/TRiC) can unfold stable misfolded polypeptide conformers and readily release them from the access ways to the cage. Reconciling earlier disparate experimental observations to ours, we present a comprehensivemodel whereby following unfolding on the upper cavity, in-cage confinement is not needed for the released intermediates to slowly reach their native state in solution. As oversticky intermediates occasionally stall the catalytic unfoldase sites, GroES mobile loops and ATP are necessary to dissociate the inhibitory species and regenerate the unfolding activity. Thus, chaperonin rings are not obligate confining antiaggregation cages. They are polypeptide unfoldases that can iteratively convert stable off-pathway conformers into functional proteins.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第18期|7199-7204|共6页
作者
Priya S.; Sharma S.K.; Sood V.Mattoo R.U.H.Finka A.Azem A.De Los Rios P.Goloubinoff P.;
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作者单位

Department of Plant Molecular Biology, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland;

Laboratory of Statistical Biophysics, School of Basic Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;

Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Molecular chaperones; Protein aggregation; Protein misfolding; Protein unfolding;

GroEL and CCT are catalytic unfoldases mediating out-of-cage polypeptide refolding without ATP

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