NASP maintains histone H3-H4 homeostasis through two distinct H3 binding modes

Hongyu Bao, Massimo Carraro, Valentin Flury, Yanhong Liu, Min Luo, Liu Chen, Anja Groth, Hongda Huang

Research output: Contribution to journalJournal articleResearchpeer-review

15 Citations (Scopus)
46 Downloads (Pure)

Abstract

Histone chaperones regulate all aspects of histone metabolism. NASP is a major histone chaperone for H3-H4 dimers critical for preventing histone degradation. Here, we identify two distinct histone binding modes of NASP and reveal how they cooperate to ensure histone H3-H4 supply. We determine the structures of a sNASP dimer, a complex of a sNASP dimer with two H3 α3 peptides, and the sNASP-H3-H4-ASF1b co-chaperone complex. This captures distinct functionalities of NASP and identifies two distinct binding modes involving the H3 α3 helix and the H3 αN region, respectively. Functional studies demonstrate the H3 αN-interaction represents the major binding mode of NASP in cells and shielding of the H3 αN region by NASP is essential in maintaining the H3-H4 histone soluble pool. In conclusion, our studies uncover the molecular basis of NASP as a major H3-H4 chaperone in guarding histone homeostasis.

Original languageEnglish
JournalNucleic Acids Research
Volume50
Issue number9
Pages (from-to)5349-5368
ISSN0305-1048
DOIs
Publication statusPublished - 2022

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cite this