title: Hsp90 regulates the dynamics of its cochaperone Sti1 and the transfer of Hsp70 between modules.
abstract: The cochaperone Sti1/Hop physically links Hsp70 and Hsp90. The protein exhibits one binding site for Hsp90 (TPR2A) and two binding sites for Hsp70 (TPR1 and TPR2B). How these sites are used remained enigmatic. Here we show that Sti1 is a dynamic, elongated protein that consists of a flexible N-terminal module, a long linker and a rigid C-terminal module. Binding of Hsp90 and Hsp70 regulates the Sti1 conformation with Hsp90 binding determining with which site Hsp70 interacts. Without Hsp90, Sti1 is more compact and TPR2B is the high-affinity interaction site for Hsp70. In the presence of Hsp90, Hsp70 shifts its preference. The linker connecting the two modules is crucial for the interaction with Hsp70 and for client activation in vivo. Our results suggest that the interaction of Hsp70 with Sti1 is tightly regulated by Hsp90 to assure transfer of Hsp70 between the modules, as a prerequisite for the efficient client handover.
authors: Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Alina
authors: A
authors: Röhl
authors: Department Chemie, Center for Nano Science, Center for integrated protein science (CIPSM) and Nanosystems Initiative München (NIM), Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany.
authors: Daniela
authors: D
authors: Wengler
authors: 1] Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany [2] Institute of Molecular Biology &Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria [3] Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Tobias
authors: T
authors: Madl
authors: 1] Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany [2] Department Chemie, Institute for Advanced Study (IAS), Technische Universität München, Lichtenbergstr. 2a, 85747 Garching, Germany.
authors: Stephan
authors: S
authors: Lagleder
authors: Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Franziska
authors: F
authors: Tippel
authors: Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Monika
authors: M
authors: Herrmann
authors: Department Chemie, Center for Nano Science, Center for integrated protein science (CIPSM) and Nanosystems Initiative München (NIM), Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany.
authors: Jelle
authors: J
authors: Hendrix
authors: Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Klaus
authors: K
authors: Richter
authors: Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Gordon
authors: G
authors: Hack
authors: Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Andreas B
authors: AB
authors: Schmid
authors: 1] Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany [2] Department Chemie, Institute for Advanced Study (IAS), Technische Universität München, Lichtenbergstr. 2a, 85747 Garching, Germany [3] Department of Chemistry, Faculty of Science, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
authors: Horst
authors: H
authors: Kessler
authors: Department Chemie, Center for Nano Science, Center for integrated protein science (CIPSM) and Nanosystems Initiative München (NIM), Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany.
authors: Don C
authors: DC
authors: Lamb
authors: Center for integrated protein science (CIPSM) at the Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Johannes
authors: J
authors: Buchner
mesh_terms: D001665:Binding Sites; D004926:Escherichia coli; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D018832:Molecular Chaperones / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D018840:HSP70 Heat-Shock Proteins; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C090869:SSA3 protein, S cerevisiae; C542289:STI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins