Hsp90 & Co. - a holding for folding

Trends Biochem Sci. 1999 Apr;24(4):136-41. doi: 10.1016/s0968-0004(99)01373-0.

Abstract

Hsp90 is an abundant molecular chaperone that is involved in the folding of a defined set of signalling molecules including steroid-hormone receptors and kinases. Recent in vitro experiments suggest that Hsp90 contains two different binding sites for non-native proteins, which allow it to combine the properties of a promiscuous chaperone with those of a dedicated folding-helper protein. Significant progress has been made in analysing co-chaperones, which form defined, substrate-dependent complexes with Hsp90 in vivo. Structural studies have identified the ATP-binding site in the N-terminal domain of Hsp90, which can be blocked by high-affinity inhibitors. Although a detailed understanding of the mechanism of Hsp90 action is still lacking, recent advances suggest that the protein is the centre of a dynamic, multifunctional and multicomponent chaperone machinery that extends the limits of protein folding in the cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Benzoquinones
  • Enzyme Inhibitors / pharmacology
  • HSP90 Heat-Shock Proteins / agonists
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / genetics*
  • HSP90 Heat-Shock Proteins / physiology
  • Lactams, Macrocyclic
  • Lactones / pharmacology
  • Macrolides
  • Models, Biological
  • Models, Molecular
  • Molecular Chaperones / physiology
  • Protein Conformation
  • Protein Folding
  • Quinones / pharmacology

Substances

  • Antibiotics, Antineoplastic
  • Benzoquinones
  • Enzyme Inhibitors
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Lactones
  • Macrolides
  • Molecular Chaperones
  • Quinones
  • monorden
  • geldanamycin