7CJ0

Crystal structure of DNAJC9 HBD in complex with H3.3-H4 dimer and MCM2 HBD

Summary for 7CJ0

• Entry DOI: 10.2210/pdb7cj0/pdb
• Descriptor: Histone H3.3, Histone H4, DNA replication licensing factor MCM2, ... (6 entities in total)
• Functional Keywords: histone chaperone, chaperone
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 75303.58

Authors

Bao, H.,Huang, H. (deposition date: 2020-07-09, release date: 2021-04-14, Last modification date: 2023-11-29)

Primary citation

Hammond, C.M.,Bao, H.,Hendriks, I.A.,Carraro, M.,Garcia-Nieto, A.,Liu, Y.,Reveron-Gomez, N.,Spanos, C.,Chen, L.,Rappsilber, J.,Nielsen, M.L.,Patel, D.J.,Huang, H.,Groth, A.
DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network.
Mol.Cell, 81:2533-2548.e9, 2021

PubMed Abstract: 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.

PubMed: 33857403
DOI: 10.1016/j.molcel.2021.03.041

Experimental method

X-RAY DIFFRACTION (2.5 Å)