Hop/Sti1 phosphorylation inhibits its co-chaperone function |
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Authors: | Alina Röhl Franziska Tippel Evelyn Bender Andreas B Schmid Klaus Richter Tobias Madl Johannes Buchner |
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Affiliation: | 1Center for Integrated Protein Science (CIPSM) at the Department Chemie, Technische Universität München, Garching, Germany;2Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany;3Institute of Molecular Biology & Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria |
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Abstract: | In eukaryotes, the molecular chaperones Hsp90 and Hsp70 are connected via the co-chaperone Sti1/Hop, which allows transfer of clients. Here, we show that the basic functions of yeast Sti1 and human Hop are conserved. These include the simultaneous binding of Hsp90 and Hsp70, the inhibition of the ATPase activity of Hsp90, and the ability to support client activation in vivo. Importantly, we reveal that both Hop and Sti1 are subject to inhibitory phosphorylation, although the sites modified and the influence of regulatory phosphorylation is species specific. Phospho-mimetic variants have a reduced ability to activate clients in vivo and different affinity for Hsp70. Hop is more tightly regulated, as phosphorylation affects also the interaction with Hsp90 and induces structural rearrangements in the core part of the protein. |
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Keywords: | co-chaperone phosphorylation regulation SAXS Sti1/Hop |
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