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

Bao, Hongyu1; Carraro, Massimo2,3; Flury, Valentin2,3; Liu, Yanhong1; Luo, Min1; Chen, Liu1; Groth, Anja2,3; Huang, Hongda1

2022-04-01

10.1093/nar/gkac303

NUCLEIC ACIDS RESEARCH   影响因子和分区

0305-1048

1362-4962

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 alpha 3 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 alpha 3 helix and the H3 alpha N region, respectively. Functional studies demonstrate the H3 alpha N-interaction represents the major binding mode of NASP in cells and shielding of the H3 alpha N 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.

SCI

英语

第一 ; 通讯

National Key R&D Program of China[2018YFC1004500] ; Chinese National Natural Science Foundation[32171206,31800619] ; Shenzhen Science and Technology Program[KQTD20190929173906742] ; Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes[2019KSYS006] ; Shenzhen Government `Peacock Plan'[Y01226136] ; Lundbeck Foundation["R198-2015-269","R313-2019-448"] ; European Research Council[724436] ; Independent Research Fund Denmark["7016-00042B","4092-00404B"] ; Novo Nordisk Foundation[NNF14CC0001]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000789028400001

OXFORD UNIV PRESS

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Southern Univ Sci & Technol, Sch Life Sci, Key Lab Mol Design Plant Cell Factory, Guangdong Higher Educ Inst,Dept Biol, Shenzhen 518055, Peoples R China
2.Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Ctr Prot Res CPR, Copenhagen, Denmark
3.Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr BRIC, Copenhagen, Denmark

Bao, Hongyu,Carraro, Massimo,Flury, Valentin,et al. NASP maintains histone H3-H4 homeostasis through two distinct H3 binding modes[J]. NUCLEIC ACIDS RESEARCH,2022.

Bao, Hongyu.,Carraro, Massimo.,Flury, Valentin.,Liu, Yanhong.,Luo, Min.,...&Huang, Hongda.(2022).NASP maintains histone H3-H4 homeostasis through two distinct H3 binding modes.NUCLEIC ACIDS RESEARCH.

Bao, Hongyu,et al."NASP maintains histone H3-H4 homeostasis through two distinct H3 binding modes".NUCLEIC ACIDS RESEARCH (2022).