Hop/Sti1 phosphorylation inhibits its co-chaperone function

Alina Röhl, Franziska Tippel, Evelyn Bender, Andreas B. Schmid, Klaus Richter, Tobias Madl, Johannes Buchner

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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. Synopsis This study shows that Hop and Sti1 are phosphorylated, and the sites and magnitude of the effects are species specific, with Hop being more tightly regulated. Phosphorylation negatively affects interaction with Hsp70. Yeast Sti1 and human Hop share highly conserved functions. Human Hsp90 is not inhibited to the same degree as yeast Hsp90 by Sti1/Hop. Phosphorylation of Hop at a unique position affects its structure. Phosphorylation of Sti1/Hop negatively affects client maturation. This study shows that Hop and Sti1 are phosphorylated, and the sites and magnitude of the effects are species specific, with Hop being more tightly regulated. Phosphorylation negatively affects interaction with Hsp70.

Original languageEnglish
Pages (from-to)240-249
Number of pages10
JournalEMBO Reports
Volume16
Issue number2
DOIs
StatePublished - 1 Feb 2015

Keywords

  • SAXS
  • Sti1/Hop
  • co-chaperone
  • phosphorylation
  • regulation

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