The origins and consequences of asymmetry in the chaperonin reaction cycle

J Mol Biol. 1995 May 26;249(1):138-52. doi: 10.1006/jmbi.1995.0285.

Abstract

The binding of nucleotides and chaperonin-10 (cpn10) to the Escherichia coli chaperonin-60 (cpn60) and their effect upon the molecular symmetry has been examined both kinetically and at equilibrium. ATP binds tightly and is hydrolysed on only one heptameric ring of the cpn60 tetradecamer at a time, thus inducing asymmetry in the cpn60 oligomer even in the absence of cpn10. In the absence of cpn10 these seven ATP molecules hydrolyse to form a cpn60:ADP7 complex in which ADP is tightly bound (Kd = 2-7 microM); further ADP binding to form a cpn60:ADP14 complex is weak (K1/2 = 2.3 mM). We conclude that symmetrical nucleotide complexes (with 14 ATP or 14 ADPs) are unstable, demonstrating negative co-operativity between the rings. When cpn60 is mixed with cpn10 and ATP the resultant cpn60:ATP7:cpn10 complex is formed rapidly (the rate constant for cpn10 association is > 4 x 10(7) M-1 s-1) and before ATP is hydrolysed (k = 0.12 s-1 per active subunit) to produce an extremely stable cpn60:ADP7:cpn10 complex. This allows ATP association on the unoccupied ring and nucleotide asymmetry in the double toroid is preserved. In "trapping" experiments, where the cpn60:ADP7:cpn10 is challenged with ATP, cpn10 was observed to dissociate at a rate identical to that of steady-state ATP hydrolysis in the presence of cpn10 (k = 0.042 s-1 per active subunit). The spontaneous decay of cpn60:ADP7:cpn10 and any of the major steady-state complexes, under conditions where free nucleotides had been removed, occurred at a rate tenfold lower than ATP hydrolysis. Since the binding of the non-hydrolysable analogue AMP-PNP was unable to induce dissociation of the co-chaperonin it was concluded that a transient state following ATP hydrolysis is necessary for the rapid dissociation of cpn10, which occurs once in every cycle. Trapping experiments using sub-stoichiometric concentrations of cpn10, relative to cpn60, show an unchanged rate of cpn10 exchange upon ATP hydrolysis, indicating that the formation of a symmetric, "football"-shaped complex in which two molecules of the co-chaperonin are bound to cpn60, is not an obligatory intermediate in the exchange process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Chaperonin 10 / chemistry
  • Chaperonin 10 / metabolism*
  • Chaperonin 60 / chemistry
  • Chaperonin 60 / metabolism*
  • Escherichia coli / metabolism
  • Hydrolysis
  • Nucleotides / chemistry
  • Protein Conformation

Substances

  • Chaperonin 10
  • Chaperonin 60
  • Nucleotides