Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT

Nat Struct Mol Biol. 2008 Jul;15(7):746-53. doi: 10.1038/nsmb.1436. Epub 2008 Jun 8.

Abstract

All chaperonins mediate ATP-dependent polypeptide folding by confining substrates within a central chamber. Intriguingly, the eukaryotic chaperonin TRiC (also called CCT) uses a built-in lid to close the chamber, whereas prokaryotic chaperonins use a detachable lid. Here we determine the mechanism of lid closure in TRiC using single-particle cryo-EM and comparative protein modeling. Comparison of TRiC in its open, nucleotide-free, and closed, nucleotide-induced states reveals that the interdomain motions leading to lid closure in TRiC are radically different from those of prokaryotic chaperonins, despite their overall structural similarity. We propose that domain movements in TRiC are coordinated through unique interdomain contacts within each subunit and, further, these contacts are absent in prokaryotic chaperonins. Our findings show how different mechanical switches can evolve from a common structural framework through modification of allosteric networks.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Chaperonin 60 / chemistry
  • Chaperonin 60 / metabolism
  • Chaperonin Containing TCP-1
  • Chaperonins / chemistry*
  • Chaperonins / metabolism
  • Chaperonins / ultrastructure
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Models, Molecular
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism

Substances

  • Chaperonin 60
  • Protein Subunits
  • Chaperonin Containing TCP-1
  • Chaperonins

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