Structural Insights into BAF47 and BAF155 Complex Formation
Structural Insights into BAF47 and BAF155 Complex Formation
复制标题
DOI：
10.1016/j.jmb.2017.04.008
复制
发表时间：
2017-06-02
影响因子：
5.6
通讯作者：
Qian, Chengmin
中科院分区：
文献类型：
--
作者：
Yan, Li;Xie, Si;Qian, Chengmin
哺乳动物 BAF 复合物是 SWI/SNF ATP 依赖性染色质重塑剂的一个亚家族，可动态调节染色质结构以调节基本细胞过程，包括基因转录、细胞周期控制和 DNA 损伤反应。到目前为止，许多不同的 BAF 复合物已被鉴定为具有来自 29 个基因的多达 15 个亚基的多态性组装体。进化上保守的BRG1/BRM、BAF47和BAF155/BAF170形成稳定的复合物，执行必需的染色质重塑活性，因此被认为是BAF复合物的核心成分。在这里，我们首先确认了 BAF155 的 SWIRM 结构域负责与 BAF47 的相互作用，然后将 BAF47 中的 SWIRM 结合区域缩小到重复 1 (RPT1) 结构域。我们进一步展示了 SWIRM/RPT1 复合物的高分辨率晶体结构。进行了广泛的诱变实验以及等温滴定量热法和核磁共振滴定，以证实在晶体结构中观察到的相互作用。总体而言，我们证明了 BAF155 SWIRM 是参与 BAF47 相互作用的模块化结构域，其功能不同于具有 DNA 结合活性的其他特征性 SWIRM 结构域。 (C) 2017 Elsevier Ltd. 保留所有权利。
Mammalian BAF complexes are a subfamily of SWI/SNF ATP-dependent chromatin remodelers that dynamically modulate chromatin structure to regulate fundamental cellular processes including gene transcription, cell cycle control, and DNA damage response. So far, many distinct BAF complexes have been identified with polymorphic assemblies of up to 15 subunits from 29 genes. The evolutionarily conserved BRG1/BRM, BAF47, and BAF155/BAF170 form a stable complex that carries out essential chromatin remodeling activity and therefore have been regarded as the core components of BAF complex. Here, we first confirmed that SWIRM domain of BAF155 is responsible for its interaction with BAF47 and then narrowed down the SWIRM-binding region in BAF47 to the Repeat 1 (RPT1) domain. We further presented the high-resolution crystal structure of SWIRM/RPT1 complex. Extensive mutagenesis experiments together with isothermal titration calorimetry and NMR titrations were performed to corroborate the interactions observed in crystal structure. Overall, we demonstrated that BAF155 SWIRM is a modular domain involved in BAF47 interaction, which is functionally distinct from other characterized SWIRM domains that possess DNA binding activity. (C) 2017 Elsevier Ltd. All rights reserved.