DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network.

Molecular cell 2021 Jun 17

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From biosynthesis to assembly into nucleosomes, histones are handed through a cascade of histone chaperones, which shield histones from non-specific interactions. Whether mechanisms exist to safeguard the histone fold during histone chaperone handover events or to release trapped intermediates is unclear. Using structure-guided and functional proteomics, we identify and characterize a histone chaperone function of DNAJC9, a heat shock co-chaperone that promotes HSP70-mediated catalysis. We elucidate the structure of DNAJC9, in a histone H3-H4 co-chaperone complex with MCM2, revealing how this dual histone and heat shock co-chaperone binds histone substrates. We show that DNAJC9 recruits HSP70-type enzymes via its J domain to fold histone H3-H4 substrates: upstream in the histone supply chain, during replication- and transcription-coupled nucleosome assembly, and to clean up spurious interactions. With its dual functionality, DNAJC9 integrates ATP-resourced protein folding into the histone supply pathway to resolve aberrant intermediates throughout the dynamic lives of histones. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Colin M Hammond, Hongyu Bao, Ivo A Hendriks, Massimo Carraro, Alberto García-Nieto, Yanhong Liu, Nazaret Reverón-Gómez, Christos Spanos, Liu Chen, Juri Rappsilber, Michael L Nielsen, Dinshaw J Patel, Hongda Huang, Anja Groth. DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network. Molecular cell. 2021 Jun 17;81(12):2533-2548.e9