Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes

Mol Endocrinol. 1993 Nov;7(11):1418-29. doi: 10.1210/mend.7.11.7906860.

Abstract

A cell-free system was used to examine heat shock protein 90 (hsp90)-progesterone receptor (PR) binding at near physiological conditions. Four major findings are presented: 1) hsp90 is required to maintain ligand binding by PR at elevated temperatures; 2) hsp70 and heat shock-related protein p60 are components of an intermediate assembly complex that precedes formation of a mature hsp90-PR complex; 3) hsp90-PR complexes are in a steady state assembly/disassembly cycle (t1/2, 5 min); and 4) hsp90 dissociation is not accelerated after progesterone binding; instead, progesterone prevents PR from forming hsp70-mediated assembly complexes. A model incorporating these findings is presented in which unliganded PR is maintained in a disactivation loop of assembly/disassembly with hsp90; hormone binding releases PR from this loop to proceed along an activation pathway.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell-Free System
  • Chaperonins
  • Chickens
  • Female
  • Heat-Shock Proteins / metabolism*
  • Ligands
  • Models, Biological*
  • Molecular Chaperones*
  • Oviducts
  • Protein Binding
  • Proteins / metabolism
  • Rabbits
  • Receptors, Progesterone / metabolism*
  • Receptors, Steroid / metabolism
  • Temperature

Substances

  • Heat-Shock Proteins
  • Ligands
  • Molecular Chaperones
  • Proteins
  • Receptors, Progesterone
  • Receptors, Steroid
  • Chaperonins