학술논문

Assembly and interaction of core subunits of BAF complexes and crystal study of the SMARCC1/SMARCE1 binary complex.
Document Type
Article
Source
Biochemical & Biophysical Research Communications. Apr2022, Vol. 599, p9-16. 8p.
Subject
*CRYSTALS
*REGULATOR genes
*PROTEIN structure
*AMINO acids
*CARCINOGENESIS
Language
ISSN
0006-291X
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. • Assembly and interaction of core subunits of BAF complexes were mainly studied by biochemical means. • The SMARCC1/SMARCD1/SMARCE1 ternary complex was co-expressed and purified successfully. • The SMARCC1/SAMRCD1/SMARCB1/SAMRCE1 tetrameric complex was co-expressed and purified successfully. • The crystals of the SMARCC1/SMARCE1 binary complex were obtained and optimized successfully. [ABSTRACT FROM AUTHOR]