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

Journal: Biochemical and biophysical research communications 2022;599():9-16

PMID: 35158202

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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/SMARCD1, SMARCC1/SMARCE1 and SMARCC1/SMARCE1 binary complex, SMARCC1/SMARCD1/SMARCE1 ternary complex SMARCC1/SAMRCD1/SMARCB1/SAMRCE1 tetrameric complexes, and obtained crystals of the SMARCC1/SMARCE1 and SMARCC1/SMARCE1 binary complex，and the SMARCC1/SMARCE1 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.

Address: College of Marine and Environmental Sciences, Tianjin University of Science and Technology, Tianjin, 300457, China. Electronic address: [email protected].; College of Marine and Environmental Sciences, Tianjin University of Science and Technology, Tianjin, 300457, China.; 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: [email protected].; Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. Electronic address: [email protected].

DOI: 10.1016/j.bbrc.2022.02.007

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MeSH Terms: Calorimetry, Chromosomal Proteins, Non-Histone, Crystallography, X-Ray, DNA-Binding Proteins, HEK293 Cells, Humans, Multiprotein Complexes, Protein Interaction Maps, SMARCB1 Protein, Transcription Factors, Ultracentrifugation