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Convergent evolution of clamp-like binding sites in diverse chaperones

Nature Structural & Molecular Biology volume 13, pages 865870 (2006) | Download Citation

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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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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. Peter C. Stirling, Andrea B. Feigl and Michel R. Leroux are in the Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada

    • Peter C Stirling
    • , Andrea B Feigl
    •  & Michel R Leroux
  2. Samuel F. Bakhoum is in the Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.

    • Samuel F Bakhoum

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The authors declare no competing financial interests.

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https://doi.org/10.1038/nsmb1153

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