The chromatin-remodelling complex SWI/SNF is highly conserved and has critical roles in various cellular processes, including transcription and DNA-damage repair^1,2. It hydrolyses ATP to remodel chromatin structure by sliding and evicting histone octamers^3,4,5,6,7,8, creating DNA regions that become accessible to other essential factors. However, our mechanistic understanding of the remodelling activity is hindered by the lack of a high-resolution structure of complexes from this family. Here we report the cryo-electron microscopy structure of Saccharomyces cerevisiae SWI/SNF bound to a nucleosome, at near-atomic resolution. In the structure, the actin-related protein (Arp) module is sandwiched between the ATPase and the rest of the complex, with the Snf2 helicase-SANT associated (HSA) domain connecting all modules. The body contains an assembly scaffold composed of conserved subunits Snf12 (also known as SMARCD or BAF60), Snf5 (also known as SMARCB1, BAF47 or INI1) and an asymmetric dimer of Swi3 (also known as SMARCC, BAF155 or BAF170). Another conserved subunit, Swi1 (also known as ARID1 or BAF250), resides in the core of SWI/SNF, acting as a molecular hub. We also observed interactions between Snf5 and the histones at the acidic patch, which could serve as an anchor during active DNA translocation. Our structure enables us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and to propose a model for how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation⁹.

染色质重塑复合物 SWI/SNF 高度保守，在各种细胞过程中具有关键作用，包括转录和 DNA 损伤修复^1,2。^{它通过滑动和逐出组蛋白八聚体3,4,5,6,7,8}来水解 ATP 以重塑染色质结构，从而创建可供其他基本因子访问的 DNA 区域。然而，由于缺乏来自该家族的复合物的高分辨率结构，我们对重塑活动的机械理解受到阻碍。在这里，我们报告了酿酒酵母的低温电子显微镜结构SWI/SNF 以接近原子的分辨率与核小体结合。在该结构中，肌动蛋白相关蛋白 (Arp) 模块夹在 ATPase 和复合物的其余部分之间，Snf2 解旋酶-SANT 相关 (HSA) 域连接所有模块。身体包含由保守亚基 Snf12（也​​称为 SMARCD 或 BAF60）、Snf5（也称为 SMARCB1、BAF47 或 INI1）和 Swi3 的不对称二聚体（也称为 SMARCC、BAF155 或 BAF170）组成的组装支架。另一个保守的亚基 Swi1（也称为 ARID1 或 BAF250）位于 SWI/SNF 的核心，充当分子中枢。我们还观察到 Snf5 和酸性斑块上的组蛋白之间的相互作用，酸性斑块可以作为活性 DNA 易位过程中的锚点。⁹ .