Abstract
A subset of essential cellular proteins requires the assistance of chaperonins (in Escherichia coli, GroEL and GroES), double-ring complexes in which the two rings act alternately to bind, encapsulate and fold a wide range of nascent or stress-denatured proteins1,2,3,4,5. This process starts by the trapping of a substrate protein on hydrophobic surfaces in the central cavity of a GroEL ring6,7,8,9,10. Then, binding of ATP and co-chaperonin GroES to that ring ejects the non-native protein from its binding sites, through forced unfolding or other major conformational changes, and encloses it in a hydrophilic chamber for folding11,12,13,14,15. ATP hydrolysis and subsequent ATP binding to the opposite ring trigger dissociation of the chamber and release of the substrate protein3. The bacteriophage T4 requires its own version of GroES, gp31, which forms a taller folding chamber, to fold the major viral capsid protein gp23 (refs 16–20). Polypeptides are known to fold inside the chaperonin complex, but the conformation of an encapsulated protein has not previously been visualized. Here we present structures of gp23–chaperonin complexes, showing both the initial captured state and the final, close-to-native state with gp23 encapsulated in the folding chamber. Although the chamber is expanded, it is still barely large enough to contain the elongated gp23 monomer, explaining why the GroEL–GroES complex is not able to fold gp23 and showing how the chaperonin structure distorts to enclose a large, physiological substrate protein.
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Data deposits
The three-dimensional reconstructions for the two binary complexes and the three ternary complexes are deposited in the EBI-MSD EMD database with accession codes EMD-1544 through to EMD-1548.
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Acknowledgements
We thank R. Westlake, D. Houldershaw and L. Wang for computing and EM support. This work was carried out at the School of Crystallography, Birkbeck College, and was supported by a Wellcome Trust programme grant, EU 3D EM Network of Excellence and 3D Repertoire grants.
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Clare, D., Bakkes, P., van Heerikhuizen, H. et al. Chaperonin complex with a newly folded protein encapsulated in the folding chamber. Nature 457, 107–110 (2009). https://doi.org/10.1038/nature07479
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DOI: https://doi.org/10.1038/nature07479
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