Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes.
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.
Smith
D F
DF
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198.
D000818:Animals; D002474:Cell-Free System; D018833:Chaperonins; D002645:Chickens; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008024:Ligands; D008954:Models, Biological; D018832:Molecular Chaperones; D010057:Oviducts; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D011980:Receptors, Progesterone / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D013696:Temperature
D006360:Heat-Shock Proteins; D008024:Ligands; D018832:Molecular Chaperones; D011506:Proteins; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D018833:Chaperonins