Assembly and interaction of core subunits of BAF complexes and crystal study of the SMARCC1/SMARCE1 binary complex

Chunming Dong; Rui Zhang; Lijun Xu; Beibei Liu; Xinlei Chu

doi:10.1016/j.bbrc.2022.02.007

Assembly and interaction of core subunits of BAF complexes and crystal study of the SMARCC1/SMARCE1 binary complex

Biochem Biophys Res Commun. 2022 Apr 9:599:9-16. doi: 10.1016/j.bbrc.2022.02.007. Epub 2022 Feb 7.

Authors

Chunming Dong¹, Rui Zhang², Lijun Xu², Beibei Liu³, Xinlei Chu⁴

Affiliations

¹ College of Marine and Environmental Sciences, Tianjin University of Science and Technology, Tianjin, 300457, China. Electronic address: mingchundongjy@tust.edu.cn.
² College of Marine and Environmental Sciences, Tianjin University of Science and Technology, Tianjin, 300457, China.
³ State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China. Electronic address: liubbei0@163.com.
⁴ Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. Electronic address: chuxinlei2014@163.com.

PMID: 35158202
DOI: 10.1016/j.bbrc.2022.02.007

Abstract

The multi-subunit ATP-dependent chromatin remodeling factor SWI/SNF complex is a fundamental regulator of gene transcription. The SWI/SNF complex in mammals, also called the BAF complex, consists of 9-12 subunits. Genomic functional studies have found that 20%-25% of human cancers are caused by mutations in genes encoding this complex. For the assembly of the BAF complex, BAF47 (SMARCB1), BAF57 (SMARCE1), BAF155 (SMARCC1)/BAF170 (SMARCC2), and BAF60 A/B/C (SMARCD1/2/3) form a core complex. However, the assembly mechanism of the BAF core subunit remains unclear. In this study, the assembly mechanism and structure of this complex and the interactions between its subunits were investigated. We co-expressed SMARCC1^(447-966)/SMARCD1^(129-471), SMARCC1^(447-966)/SMARCE1^(210-284) and SMARCC1^(862-966)/SMARCE1^(210-284) binary complex, SMARCC1^(862-966)/SMARCD1^(129-471)/SMARCE1^(210-284) ternary complex SMARCC1^(353-966)/SAMRCD1^(129-471)/SMARCB1^(110-385)/SAMRCE1^(210-284) tetrameric complexes, and obtained crystals of the SMARCC1^(862-966)/SMARCE1^(210-284) and SMARCC1^(883-966)/SMARCE1^(210-284) binary complex，and the SMARCC1^(883-966)/SMARCE1^(210-284) crystal received a set of diffraction data of 3.2 Å. Our experimental results demonstrate the assembly mechanism between the core subunit quaternary complexes of the BAF complex and the interacting amino acid fragment regions and the SMARCC1/SMARCE1 optimal amino acid fragment binary complex crystals. Our study provides a theoretical basis for the development of cancer and related drug research based on protein structure.

Keywords: BAF complex; Chromatin remodeling; SMARCC1/SAMRCD1/SMARCB1/SAMRCE1; SMARCC1/SMARCE1 binary complex; SWI/SNF complex; Ternary complex.

Publication types

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

MeSH terms

Calorimetry
Chromosomal Proteins, Non-Histone / chemistry*
Chromosomal Proteins, Non-Histone / genetics
Chromosomal Proteins, Non-Histone / metabolism
Crystallography, X-Ray
DNA-Binding Proteins / chemistry*
DNA-Binding Proteins / metabolism
HEK293 Cells
Humans
Multiprotein Complexes / chemistry
Multiprotein Complexes / metabolism*
Protein Interaction Maps
SMARCB1 Protein / genetics
SMARCB1 Protein / metabolism
Transcription Factors / chemistry*
Transcription Factors / genetics
Transcription Factors / metabolism
Ultracentrifugation

Substances

Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Multiprotein Complexes
SMARCB1 Protein
SMARCB1 protein, human
SMARCC1 protein, human
SMARCD1 protein, human
SMARCE1 protein, human
Transcription Factors