title: Hsp90 chaperones protein folding in vitro.
abstract: The heat-shock protein Hsp90 is the most abundant constitutively expressed stress protein in the cytosol of eukaryotic cells, where it participates in the maturation of other proteins, modulation of protein activity in the case of hormone-free steroid receptors, and intracellular transport of some newly synthesized kinases. A feature of all these processes could be their dependence on the formation of protein structure. If Hsp90 is a molecular chaperone involved in maintaining a certain subset of cellular proteins in an inactive form, it should also be able to recognize and bind non-native proteins, thereby influencing their folding to the native state. Here we investigate whether Hsp90 can influence protein folding in vitro and show that Hsp90 suppresses the formation of protein aggregates by binding to the target proteins at a stoichiometry of one Hsp90 dimer to one or two substrate molecule(s). Furthermore, the yield of correctly folded and functional protein is increased significantly. The action of Hsp90 does not depend on the presence of nucleoside triphosphates, so it may be that Hsp90 uses a novel molecular mechanism to assist protein folding in vivo.
authors.affiliation: Zentrum Biochemie/Abteilung Biochemie II, Universität Göttingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wiech
authors.forename: J
authors.initials: J
authors.lastname: Buchner
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: U
authors.initials: U
authors.lastname: Jakob
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002417:Cattle; D002950:Citrate (si)-Synthase / Q000737:chemistry; D003402:Creatine Kinase / Q000276:immunology; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D010179:Pancreas / Q000737:chemistry; D011487:Protein Conformation / Q000187:drug effects*; D011489:Protein Denaturation
chemical_list: D000911:Antibodies, Monoclonal; D006360:Heat-Shock Proteins; D007140:Immunoglobulin Fab Fragments; D046911:Macromolecular Substances; D002950:Citrate (si)-Synthase; D003402:Creatine Kinase