Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains

Benjamin L. Piette, Nader Alerasool, Zhen Yuan Lin, Jessica Lacoste, Mandy Hiu Yi Lam, Wesley Wei Qian, Stephanie Tran, Brett Larsen, Eric Campos, Jian Peng, Anne Claude Gingras, Mikko Taipale

Research output: Contribution to journalArticlepeer-review

Abstract

Hsp70s comprise a deeply conserved chaperone family that has a central role in maintaining protein homeostasis. In humans, Hsp70 client specificity is provided by 49 different co-factors known as J domain proteins (JDPs). However, the cellular function and client specificity of JDPs have largely remained elusive. We have combined affinity purification-mass spectrometry (AP-MS) and proximity-dependent biotinylation (BioID) to characterize the interactome of all human JDPs and Hsp70s. The resulting network suggests specific functions for many uncharacterized JDPs, and we establish a role of conserved JDPs DNAJC9 and DNAJC27 in histone chaperoning and ciliogenesis, respectively. Unexpectedly, we find that the J domain of DNAJC27 but not of other JDPs can fully replace the function of endogenous DNAJC27, suggesting a previously unappreciated role for J domains themselves in JDP specificity. More broadly, our work expands the role of the Hsp70-regulated proteostasis network and provides a platform for further discovery of JDP-dependent functions.

Original languageEnglish (US)
Pages (from-to)2549-2565.e8
JournalMolecular cell
Volume81
Issue number12
DOIs
StatePublished - Jun 17 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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