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Title: | Hsp90 regulates the dynamics of its cochaperone Sti1 and the transfer of Hsp70 between modules | Authors: | Roehl, Alina Wengler, Daniela Madl, Tobias Lagleder, Stephan Tippel, Franziska Herrmann, Monika HENDRIX, Jelle Richter, Klaus Hack, Gordon Schmid, Andreas B. Kessler, Horst Lamb, Don C. Buchner, Johannes |
Issue Date: | 2015 | Publisher: | NATURE PUBLISHING GROUP | Source: | NATURE COMMUNICATIONS, 6 (Art N° 6655) | 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. | Notes: | [Roehl, Alina; Madl, Tobias; Lagleder, Stephan; Tippel, Franziska; Herrmann, Monika; Richter, Klaus; Hack, Gordon; Schmid, Andreas B.; Kessler, Horst; Buchner, Johannes] Tech Univ Munich, Dept Chem, Ctr Integrated Prot Sci CIPSM, D-85747 Garching, Germany. [Wengler, Daniela; Hendrix, Jelle; Lamb, Don C.] Univ Munich, Dept Chem, Ctr Nano Sci, Ctr Integrated Prot Sci CIPSM, D-81377 Munich, Germany. [Wengler, Daniela; Hendrix, Jelle; Lamb, Don C.] Univ Munich, NIM, D-81377 Munich, Germany. [Madl, Tobias] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria. [Madl, Tobias] Helmholtz Zentrum Munchen, Inst Biol Struct, D-85764 Neuherberg, Germany. [Lagleder, Stephan; Kessler, Horst] Tech Univ Munich, IAS, Dept Chem, D-85747 Garching, Germany. [Kessler, Horst] King Abdulaziz Univ, Fac Sci, Dept Chem, Jeddah 21589, Saudi Arabia. | Document URI: | http://hdl.handle.net/1942/27263 | e-ISSN: | 2041-1723 | DOI: | 10.1038/ncomms7655 | ISI #: | 000353697200001 | Rights: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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