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

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(210284) binary complex,and the SMARCC1(883-966)/SMARCE1(210-284) crystal received a set of diffraction data of 3.2 A. 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. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study investigates the assembly mechanism and structure of the multi-subunit ATP-dependent chromatin remodeling factor SWI/SNF complex, as well as the interactions between its subunits. Experimental results demonstrate the assembly mechanism of the core subunit quaternary complexes of the BAF complex and provide crystal structures of corresponding binary complexes. This study provides a theoretical basis for cancer and drug research based on protein structure.