多亚基ATP依赖性染色质重塑因子SWI/SNF复合物是基因转录的基本调节因子。哺乳动物的SWI/SNF复合物,也称为BAF复合体,由9-12个亚基组成。基因功能研究发现,20%-25%的人类癌症是由编码这种复合物的基因突变引起的。对于BAF综合体的组装,BAF47(SMARCB1),BAF57(SMARCE1),BAF155(SMARCC1)/BAF170(SMARCC2),和BAF60A/B/C(SMARCD1/2/3)形成核心复合物。然而,BAF核心亚基的组装机制尚不清楚.在这项研究中,研究了该复合物的组装机制和结构及其亚基之间的相互作用。我们共表达SMARCC1(447-966)/SMARCD1(129-471),SMARCC1(447-966)/SMARCE1(210-284)和SMARCC1(862-966)/SMARCE1(210-284)二元复合物,SMARCC1(862-966)/SMARCD1(129-471)/SMARCE1(210-284)三元复合物SMARCC1(353-966)/SAMRCD1(129-471)/SMARCB1(110-385)/SAMRCE1(210-284)四聚体复合物,并获得了SMARCC1(862-966)/SMARCE1(210-284)和SMARCC1(883-966)/SMARCE1(210-284)二元复合物的晶体,以及SMARCC1(883-966)/SMARCE1(210-284)晶体的一组衍射数据为3.2。我们的实验结果证明了BAF复合物的核心亚基四元复合物与相互作用的氨基酸片段区域和SMARCC1/SMARCE1最佳氨基酸片段二元复合物晶体之间的组装机制。我们的研究为基于蛋白质结构的癌症开发和相关药物研究提供了理论依据。
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.