Hsp90 & Co. - a holding for folding.
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.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D016227:Benzoquinones; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000819:agonists / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D047029:Lactams, Macrocyclic; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D008954:Models, Biological; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000502:physiology; D011487:Protein Conformation; D017510:Protein Folding; D011809:Quinones / Q000494:pharmacology