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Convergent evolution of clamp-like binding sites in diverse chaperones

Nature Structural & Molecular Biology volume 13, pages 865–870 (2006)Cite this article

Abstract

Molecular chaperones have evolved diverse tertiary and quaternary structures to stabilize non-native polypeptides and facilitate their transition to the native state. Indeed, different families of chaperones lack sequence similarity, and few are represented ubiquitously in all three domains of life. Despite their discrete evolutionary paths, recent crystal structures reveal that many chaperones use seemingly convergent strategies to bind non-native proteins. This crystallographic evidence shows, or strongly suggests, that chaperones including prefoldin, Skp, trigger factor, Hsp40 and Hsp90 have clamp-like structural features used to grip substrate proteins. We explore the notion that clamp-like structures are evolutionarily favored by both ATP-dependent and ATP-independent molecular chaperones. Presumably, clamps present a multivalent binding surface ideal for protecting unstable protein conformers until they reach the native state or are transferred to another component of the folding machinery.

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Figure 1: Crystal structures of trigger factor and proteins with trigger factor–like folds.
Figure 2: E. coli Hsp70 (DnaK) and S. cerevisiae Hsp40 (Sis1) structures.
Figure 3: Structural comparison of prefoldin, Skp and Tim9–Tim10.
Figure 4: Hsp90 adopts a dimeric clamp-like structure.

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Acknowledgements

We thank M. Sousa for the complete model of the Skp trimer and apologize to those colleagues whose work is not cited due to space restrictions. M.R.L. acknowledges funding support from the Canadian Institutes for Health Research (CIHR). M.R.L. holds scholar awards from CIHR and the Michael Smith Foundation for Health Research (MSFHR), and P.C.S. holds graduate scholarships from MSFHR and the Natural Sciences and Engineering Research Council of Canada.

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  1. the Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, V5A 1S6, British Columbia, Canada

    Peter C Stirling, Andrea B Feigl & Michel R Leroux

  2. the Department of Biochemistry, Dartmouth Medical School, Hanover, 03755, New Hampshire, USA

    Samuel F Bakhoum

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Correspondence to Michel R Leroux.

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Stirling, P., Bakhoum, S., Feigl, A. et al. Convergent evolution of clamp-like binding sites in diverse chaperones. Nat Struct Mol Biol 13, 865–870 (2006). https://doi.org/10.1038/nsmb1153

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