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Licensed Unlicensed Requires Authentication Published by De Gruyter January 16, 2018

Interaction of the middle domains stabilizes Hsp90α dimer in a closed conformation with high affinity for p23

  • Kamil Synoradzki , Przemyslaw Miszta , Egidijus Kazlauskas , Aurelija Mickevičiūtė , Vilma Michailovienė , Daumantas Matulis , Slawomir Filipek and Pawel Bieganowski EMAIL logo
From the journal Biological Chemistry


The human genome encodes two highly similar cytosolic Hsp90 proteins called isoforms Hsp90α and Hsp90β. Of the 300 client proteins for Hsp90 identified so far only a handful interact specifically with one Hsp90 isoform. Here we report for the first time that Hsp90 cochaperone p23 binds preferentially to Hsp90α and that this interaction is mediated by the middle domain of Hsp90α. Based on the homology modeling, we infer that the middle domains in the Hsp90α dimer bind stronger with each other than in the Hsp90β dimer. Therefore, compared to Hsp90β, Hsp90α may adopt closed conformation more easily. Hsp90 interacts with p23 in the closed conformation. Hsp90α binds human recombinant p23 about three times stronger than Hsp90β but with significantly smaller exothermic enthalpy as determined by isothermal titration calorimetry of direct binding between the purified proteins. As p23 binds to Hsp90 in a closed conformation, stabilization of the Hsp90α dimer in the closed conformation by its middle domains explains preference of p23 to this Hsp90 isoform.


This work was supported by the Polish National Science Centre grant no. NN303818640 and 2016/23/B/NZ6/02536. The sponsor played no role in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. The authors declare no conflicts of interest.


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Received: 2017-5-31
Accepted: 2017-12-14
Published Online: 2018-1-16
Published in Print: 2018-3-28

©2018 Walter de Gruyter GmbH, Berlin/Boston

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