Essential function of the built-in lid in the allosteric regulation of eukaryotic and archaeal chaperonins

Nat Struct Mol Biol. 2007 May;14(5):432-40. doi: 10.1038/nsmb1236. Epub 2007 Apr 29.

Abstract

Chaperonins are allosteric double-ring ATPases that mediate cellular protein folding. ATP binding and hydrolysis control opening and closing of the central chaperonin chamber, which transiently provides a protected environment for protein folding. During evolution, two strategies to close the chaperonin chamber have emerged. Archaeal and eukaryotic group II chaperonins contain a built-in lid, whereas bacterial chaperonins use a ring-shaped cofactor as a detachable lid. Here we show that the built-in lid is an allosteric regulator of group II chaperonins, which helps synchronize the subunits within one ring and, to our surprise, also influences inter-ring communication. The lid is dispensable for substrate binding and ATP hydrolysis, but is required for productive substrate folding. These regulatory functions of the lid may serve to allow the symmetrical chaperonins to function as 'two-stroke' motors and may also provide a timer for substrate encapsulation within the closed chamber.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Allosteric Regulation*
  • Chaperonins / chemistry*
  • Evolution, Molecular
  • Kinetics
  • Protein Conformation
  • Protein Folding
  • Protein Subunits

Substances

  • Protein Subunits
  • Adenosine Triphosphate
  • Chaperonins