title: Conformational selection in substrate recognition by Hsp70 chaperones.
abstract: Hsp70s are molecular chaperones involved in the folding and assembly of proteins. They recognize hydrophobic amino acid stretches in their substrate binding groove. However, a detailed understanding of substrate specificity is still missing. Here, we use the endoplasmic reticulum-resident Hsp70 BiP to identify binding sites in a natural client protein. Two sites are mutually recognized and form stable Hsp70-substrate complexes. In silico and in vitro analyses revealed an extended substrate conformation as a crucial factor for interaction and show an unexpected plasticity of the substrate binding groove. The basic binding mechanism is conserved among different Hsp70s.
authors.affiliation: Department Chemie, Technische Universität München, 85748 Garching, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Marcinowski
authors.forename: Mathias
authors.initials: M
authors.lastname: Rosam
authors.forename: Christine
authors.initials: C
authors.lastname: Seitz
authors.forename: Johannes
authors.initials: J
authors.lastname: Elferich
authors.forename: Julia
authors.initials: J
authors.lastname: Behnke
authors.forename: Claudia
authors.initials: C
authors.lastname: Bello
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Feige
authors.forename: Christian F W
authors.initials: CF
authors.lastname: Becker
authors.forename: Iris
authors.initials: I
authors.lastname: Antes
authors.forename: Johannes
authors.initials: J
authors.lastname: Buchner
mesh_terms: D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C063842:dnaK protein, E coli