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The crystal structure of the asymmetric GroEL–GroES–(ADP)7 chaperonin complex

Nature volume 388, pages 741–750 (1997)Cite this article

Abstract

Chaperonins assist protein folding with the consumption of ATP. They exist as multi-subunit protein assemblies comprising rings of subunits stacked back to back. In Escherichia coli, asymmetric intermediates of GroEL are formed with the co-chaperonin GroES and nucleotides bound only to one of the seven-subunit rings (the cis ring) and not to the opposing ring (the trans ring). The structure of the GroEL–GroES–(ADP)7 complex reveals how large en bloc movements of the cis ring's intermediate and apical domains enable bound GroES to stabilize a folding chamber with ADP confined to the cis ring. Elevation and twist of the apical domains double the volume of the central cavity and bury hydrophobic peptide-binding residues in the interface with GroES, as well as between GroEL subunits, leaving a hydrophilic cavity lining that is conducive to protein folding. An inward tilt of the cis equatorial domain causes an outward tilt in the trans ring that opposes the binding of a second GroES. When combined with new functional results, this negative allosteric mechanism suggests a model for an ATP-driven folding cycle that requires a double toroid.

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Figure 1: Overall architecture and dimensions of the GroEL–GroES complex.
Figure 2: The components of the GroEL–GroES complex.
Figure 3: The components of the GroEL–GroES complex.
Figure 4: The components of the GroEL–GroES complex.
Figure 5: The components of the GroEL–GroES complex.
Figure 6: Nucleotide-binding site in the cis ring of the GroEL–GroES complex.
Figure 7: Nucleotide-binding site in the cis ring of the GroEL–GroES complex.
Figure 8: Nucleotide-binding site in the cis ring of the GroEL–GroES complex.
Figure 9: Inter-subunit contacts in the cis ring of the GroEL–GroES complex.
Figure 10: Inter-subunit contacts in the cis ring of the GroEL–GroES complex.
Figure 11: Inter-subunit contacts in the cis ring of the GroEL–GroES complex.
Figure 12: The change in the central cavity.
Figure 13: The change in the central cavity.
Figure 14: The change in the central cavity.
Figure 15: Schematic (exaggerated) representation of the en bloc tilt of the equatorial domains and the subsequent deformation of the equato.

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Acknowledgements

We thank J. Geiger, G. Van Duyne, R. Gaudet and G. Meinke for assistance during data collection; L. Berman (X25-NSLS at Brookhaven), S. Ealick (CHESS at Cornell) and H. Bartunik (DESY at Hamburg) for access to and help with their respective synchrotron X-ray sources; P. Adams and A. Brunger for suggestions on structure refinement; J. Hunt and J. Deisenhofer for refined GroES coordinates; and members of the Sigler and Horwich labs (especially D. Boisvert) for advice and discussions. This work was supported in part by NIH grants to P.B.S. and A.L.H., and the Yale Center for Structural Biology.

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Authors and Affiliations

  1. The Department of Molecular Biophysics and Biochemistry, The Howard Hughes Medical Institute, Yale University, 260 Whitney Avenue

    Zhaohui Xu & Paul B. Sigler

  2. The Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06510, Connecticut, USA

    Arthur L. Horwich

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Xu, Z., Horwich, A. & Sigler, P. The crystal structure of the asymmetric GroEL–GroES–(ADP)7 chaperonin complex. Nature 388, 741–750 (1997). https://doi.org/10.1038/41944

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