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primary topic: Ydj1 interaction at nucleotide-binding-domain of yeast Ssa1 impacts Hsp90 collaboration and client maturation

Ydj1 interaction at nucleotide-binding-domain of yeast Ssa1 impacts Hsp90 collaboration and client maturation
type: AcademicArticle
type: Article
abstract: Hsp90 constitutes one of the major chaperone machinery in the cell. The Hsp70 assists Hsp90 in its client maturation though the underlying basis of the Hsp70 role remains to be explored. In the present study, using S. cerevisiae strain expressing Ssa1 as sole Ssa Hsp70, we identified novel mutations in the nucleotide-binding domain of yeast Ssa1 Hsp70 (Ssa1-T175N and Ssa1-D158N) that adversely affect the maturation of Hsp90 clients v-Src and Ste11. The identified Ssa1 amino acids critical for Hsp90 function were also found to be conserved across species such as in E.coli DnaK and the constitutive Hsp70 isoform (HspA8) in humans. These mutations are distal to the C-terminus of Hsp70, that primarily mediates Hsp90 interaction through the bridge protein Sti1, and proximal to Ydj1 (Hsp40 co-chaperone of Hsp70 family) binding region. Intriguingly, we found that the bridge protein Sti1 is critical for cellular viability in cells expressing Ssa1-T175N (A1-T175N) or Ssa1-D158N (A1-D158N) as sole Ssa Hsp70. The growth defect was specific for sti1Δ, as deletion of none of the other Hsp90 co-chaperones showed lethality in A1-T175N or A1-D158N. Mass-spectrometry based whole proteome analysis of A1-T175N cells lacking Sti1 showed an altered abundance of various kinases and transcription factors suggesting compromised Hsp90 activity. Further proteomic analysis showed that pathways involved in signaling, signal transduction, and protein phosphorylation are markedly downregulated in the A1-T175N upon repressing Sti1 expression using doxycycline regulatable promoter. In contrast to Ssa1, the homologous mutations in Ssa4 (Ssa4-T175N/D158N), the stress inducible Hsp70 isoform, supported cell growth even in the absence of Sti1. Overall, our data suggest that Ydj1 competes with Hsp90 for binding to Hsp70, and thus regulates Hsp90 interaction with the nucleotide-binding domain of Hsp70. The study thus provides new insight into the Hsp70-mediated regulation of Hsp90 and broadens our under…
date: 2022-11-09
volume: 18
issue: 11
is part of: PLoS genetics
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
subject: QR Microbiology

Public Library of Science
type: Organization

PLoS genetics
type: Collection
issn: 15537404

Deepak Sharma
type: Person
given name: Deepak
family name: Sharma

Jyoti Guleria
type: Person
given name: Jyoti
family name: Guleria

Thomas Nystrom
type: Person
given name: Thomas
family name: Nystrom

Prashant Singh
type: Person
given name: Prashant
family name: Singh

Navinder Kumar
type: Person
given name: Navinder
family name: Kumar

Abhirupa Ghosh
type: Person
given name: Abhirupa
family name: Ghosh

Satinderdeep Kaur
type: Person
given name: Satinderdeep
family name: Kaur

Pradeep Kumar
type: Person
given name: Pradeep
family name: Kumar

Deepika Gaur
type: Person
given name: Deepika
family name: Gaur

Nikhil Malik
type: Person
given name: Nikhil
family name: Malik

Sudipto Saha
type: Person
given name: Sudipto
family name: Saha

HTML Summary of #3145 Ydj1 interaction at nucleotide-binding-domain of yeast Ssa1 impacts Hsp90 collaboration and client maturation
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primary topic: Ydj1 interaction at nucleotide-binding-domain of yeast Ssa1 impacts Hsp90 collaboration and client maturation

QR Microbiology
type: Concept