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The Yeast Hsp70 Cochaperone Ydj1 Regulates Functional Distinction of Ssa Hsp70s in the Hsp90 Chaperoning Pathway

Gaur, Deepika and Singh, Prashant and Guleria, Jyoti and Gupta, Arpit and Kaur, Satinderdeep and Sharma, Deepak (2020) The Yeast Hsp70 Cochaperone Ydj1 Regulates Functional Distinction of Ssa Hsp70s in the Hsp90 Chaperoning Pathway. Genetics, 215 (3). pp. 683-698. ISSN 0016-6731. https://resolver.caltech.edu/CaltechAUTHORS:20200603-140947149

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Abstract

Heat-shock protein (Hsp) 90 assists in the folding of diverse sets of client proteins including kinases and growth hormone receptors. Hsp70 plays a major role in many Hsp90 functions by interacting and modulating conformation of its substrates before being transferred to Hsp90s for final maturation. Each eukaryote contains multiple members of the Hsp70 family. However, the role of different Hsp70 isoforms in Hsp90 chaperoning actions remains unknown. Using v-Src as an Hsp90 substrate, we examined the role of each of the four yeast cytosolic Ssa Hsp70s in regulating Hsp90 functions. We show that the strain expressing stress-inducible Ssa3 or Ssa4, and the not constitutively expressed Ssa1 or Ssa2, as the sole Ssa Hsp70 isoform reduces v-Src-mediated growth defects. The study shows that although different Hsp70 isoforms interact similarly with Hsp90s, v-Src maturation is less efficient in strains expressing Ssa4 as the sole Hsp70. We further show that the functional distinction between Ssa2 and Ssa4 is regulated by its C-terminal domain. Further studies reveal that Ydj1, which is known to assist substrate transfer to Hsp70s, interacts relatively weakly with Ssa4 compared with Ssa2, which could be the basis for poor maturation of the Hsp90 client in cells expressing stress-inducible Ssa4 as the sole Ssa Hsp70. The study thus reveals a novel role of Ydj1 in determining the functional distinction among Hsp70 isoforms with respect to the Hsp90 chaperoning action.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1534/genetics.120.303190DOIArticle
https://doi.org/10.25386/genetics.12136941DOISupplmental Material
Alternate Title:Yeast Hsp70 Co-chaperone Ydj1 Regulates Functional Distinction of Ssa Hsp70s in the Hsp90 Chaperoning Pathway
Additional Information:© 2020 Genetics Society of America. Received September 27, 2019. Accepted April 13, 2020. We thank Daniel Masison for critical reading of the manuscript, Kevin Morano for providing the PRE-lacZ plasmid as a kind gift, and Jeffrey Brodsky for providing the anti-Sse1 antibody as a kind gift. The work was supported by the Council of Scientific and Industrial Research, India and a Rapid Grant for Young Investigators, Department of Biotechnology, India grant (BT/PR6463/GBD/27/420/2012). The authors declare that they have no conflicts of interest.
Funders:
Funding AgencyGrant Number
Council of Scientific and Industrial Research (India)UNSPECIFIED
Department of Biotechnology (India)BT/PR6463/GBD/27/420/2012
Subject Keywords:Hsp70; Hsp40; Hsp90; v-Src
Issue or Number:3
Record Number:CaltechAUTHORS:20200603-140947149
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200603-140947149
Official Citation:The Yeast Hsp70 Cochaperone Ydj1 Regulates Functional Distinction of Ssa Hsp70s in the Hsp90 Chaperoning Pathway. Deepika Gaur, Prashant Singh, Jyoti Guleria, Arpit Gupta, Satinderdeep Kaur and Deepak Sharma. GENETICS July 1, 2020 vol. 215 no. 3, 683-698; https://doi.org/10.1534/genetics.120.303190
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103679
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Jun 2020 21:44
Last Modified:15 Jul 2020 20:34

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