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 di fferent binding sites for non-native proteins, which allow it to combine th e properties of a promiscuous chaperone with those of a dedicated folding-h elper protein. Significant progress has been made in analysing co-chaperone s, which form defined, substrate-dependent complexes with Hsp90 in vivo. St ructural studies have identified the ATP-binding site in the N-terminal dom ain of Hsp90, which can be blocked by high-affinity inhibitors. Although a detailed understanding of the mechanism of Hsp90 action is still lacking, r ecent advances suggest that the protein is the centre of a dynamic, multifu nctional and multicomponent chaperone machinery that extends the limits of protein folding in the cell.