Structure of nucleosome-bound human BAF complex

Shuang He; Zihan Wu; Yuan Tian; Zishuo Yu; Jiali Yu; Xinxin Wang; Jie Li; Bijun Liu; Yanhui Xu

doi:10.1126/science.aaz9761

Structure of nucleosome-bound human BAF complex

Science. 2020 Feb 21;367(6480):875-881. doi: 10.1126/science.aaz9761. Epub 2020 Jan 30.

Authors

Shuang He^#^{1

2}, Zihan Wu^#^{1

2}, Yuan Tian^#^{1

2}, Zishuo Yu^{1

2}, Jiali Yu^{1

2}, Xinxin Wang^{1

2}, Jie Li¹, Bijun Liu¹, Yanhui Xu^{3

2

4

5}

Affiliations

¹ Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China.
² The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, China, Department of Systems Biology for Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
³ Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China. xuyh@fudan.edu.cn.
⁴ Human Phenome Institute, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
⁵ CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.

^# Contributed equally.

PMID: 32001526
DOI: 10.1126/science.aaz9761

Abstract

Mammalian SWI/SNF family chromatin remodelers, BRG1/BRM-associated factor (BAF) and polybromo-associated BAF (PBAF), regulate chromatin structure and transcription, and their mutations are linked to cancers. The 3.7-angstrom-resolution cryo-electron microscopy structure of human BAF bound to the nucleosome reveals that the nucleosome is sandwiched by the base and the adenosine triphosphatase (ATPase) modules, which are bridged by the actin-related protein (ARP) module. The ATPase motor is positioned proximal to nucleosomal DNA and, upon ATP hydrolysis, engages with and pumps DNA along the nucleosome. The C-terminal α helix of SMARCB1, enriched in positively charged residues frequently mutated in cancers, mediates interactions with an acidic patch of the nucleosome. AT-rich interactive domain-containing protein 1A (ARID1A) and the SWI/SNF complex subunit SMARCC serve as a structural core and scaffold in the base module organization, respectively. Our study provides structural insights into subunit organization and nucleosome recognition of human BAF complex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / chemistry
Adenosine Triphosphate / metabolism
Chromatin Assembly and Disassembly*
Chromosomal Proteins, Non-Histone / chemistry*
Chromosomal Proteins, Non-Histone / genetics
Cryoelectron Microscopy
DNA Helicases / chemistry*
DNA-Binding Proteins
Humans
Hydrolysis
Mutation
Neoplasms / genetics
Nuclear Proteins / chemistry*
Nucleosomes / chemistry*
Protein Conformation, alpha-Helical
SMARCB1 Protein / chemistry*
Transcription Factors / chemistry*
Transcription Factors / genetics

Substances

ARID1A protein, human
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Nuclear Proteins
Nucleosomes
SMARCA2 protein, human
SMARCB1 Protein
SMARCB1 protein, human
SWI-SNF-B chromatin-remodeling complex
Transcription Factors
Adenosine Triphosphate
Adenosine Triphosphatases
SMARCA4 protein, human
DNA Helicases