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Release of both native and non-native proteins from a cis-only GroEL ternary complex

Nature volume 383, pages 9699 (05 September 1996) | Download Citation

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Abstract

PROTEIN folding by the double-ring chaperonin GroEL is initiated in cis ternary complexes, in which polypeptide is sequestered in the central channel of a GroEL ring, capped by the co-chaperonin GroES1–3. The cis ternary complex is dissociated (half-life of ˜15 s) by trans-sided ATP hydrolysis, which triggers release of GroES4–6. For the substrate protein rhodanese, only ˜15% of cis-localized molecules attain their native form before hydrolysis2,7. A major question concerning the GroEL mechanism is whether both native and non-native forms are released from the cis complex. Here we address this question using a 'cis-only' mixed-ring GroEL complex that binds polypeptide and GroES on only one of its two rings. This complex mediates refolding of rhodanese but, as with wild-type GroEL, renaturation is quenched by addition of mutant GroEL 'traps', which bind but do not release polypeptide substrate7,8. This indicates that non-native forms are released from the cis complex. Quenching of refolding by traps was also observed under physiological conditions, both in undiluted Xenopus oocyte extract and in intact oocytes. We conclude that release of non-native forms from GroEL in vivo allows a kinetic partitioning among various chaperones and proteolytic components, which determines both the conformation and lifetime of a protein.

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Author information

Affiliations

  1. Department of Genetics, Yale University School of Medicine, Boyer Center, 295 Congress Avenue, New Haven, Connecticut 06510, USA

    • Steven G. Burston
    •  & Wayne A. Fenton
  2. Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center, 295 Congress Avenue, New Haven, Connecticut 06510, USA

    • Jonathan S. Weissman
    • , George W. Farr
    •  & Arthur L. Norwich
  3. Present address: Department of Pharmacology, UCSF School of Medicine, San Francisco, California 94143, USA

    • Jonathan S. Weissman

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https://doi.org/10.1038/383096a0

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