Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains.
Mol Cell
; 81(12): 2549-2565.e8, 2021 06 17.
Article
em En
| MEDLINE
| ID: mdl-33957083
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Choque Térmico HSP70
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Proteínas de Choque Térmico HSP40
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Domínios e Motivos de Interação entre Proteínas
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article