Structure of an actin-related subcomplex of the SWI/SNF chromatin remodeler
Structure of an actin-related subcomplex of the SWI/SNF chromatin remodeler
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DOI：
10.1073/pnas.1215379110
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发表时间：
2013-02-26
影响因子：
11.1
通讯作者：
Hill, Christopher P.
中科院分区：
文献类型：
--
作者：
Schubert, Heidi L.;Wittmeyer, Jacqueline;Hill, Christopher P.
将DNA包装成核小体结构限制了转录和DNA修复等模板化过程的进行。因此，核小体的重新定位或弹射对于包括基因表达在内的调控事件至关重要。这种活性是由染色质重塑复合体或重构体提供的，染色质重塑复合体通常是使用ATPase亚单位来转运DNA的大的多亚单位复合体。许多重构体含有一对或多聚体的肌动蛋白相关蛋白(ARP)，它们与催化的ATPase亚单位内的解旋酶SANT相关(HSA)结构域接触，被认为调节ATPase的活性。在这里，我们确定了SWI/SNF重构体中四蛋白亚复合体的结构，该亚复合体包括Snf2 HSA结构域Arp7、Arp9和Tyl转座抑制物基因102(Rtt102)。令人惊讶的是，与典型的肌动蛋白-肌动蛋白结合不同，这两个Arp像勺子一样堆积在一起，跨越HSA结构域，形成一个92埃长的螺旋。ARP-HSA的相互作用使人想起肌动蛋白与许多结合伙伴之间的接触，与Arp2/3复合体中的作用有很大不同。Rtt102以高度延伸的构象包裹在复合体的一侧，与两个Arp接触，因此稳定了复合体，但功能是将含有Snf2 ATPase结构域的复合体的重塑和ATPase活性降低约2.4倍。因此，我们的结构为开发重构体功能的模型提供了基础，包括Arps和ATPase转位活性之间的偶联机制。
The packaging of DNA into nucleosomal structures limits access for templated processes such as transcription and DNA repair. The repositioning or ejection of nucleosomes is therefore critically important for regulated events, including gene expression. This activity is provided by chromatin remodeling complexes, or remodelers, which are typically large, multisubunit complexes that use an ATPase subunit to translocate the DNA. Many remodelers contain pairs or multimers of actin-related proteins (ARPs) that contact the helicase-SANT-associated (HSA) domain within the catalytic ATPase subunit and are thought to regulate ATPase activity. Here, we determined the structure of a four-protein subcomplex within the SWI/SNF remodeler that comprises the Snf2 HSA domain, Arp7, Arp9, and repressor of Tyl transposition, gene 102 (Rtt102). Surprisingly, unlike characterized actin-actin associations, the two ARPs pack like spoons and straddle the HSA domain, which forms a 92-angstrom-long helix. The ARP-HSA interactions are reminiscent of contacts between actin and many binding partners and are quite different from those in the Arp2/3 complex. Rtt102 wraps around one side of the complex in a highly extended conformation that contacts both ARPs and therefore stabilizes the complex, yet functions to reduce by similar to 2.4-fold the remodeling and ATPase activity of complexes containing the Snf2 ATPase domain. Thus, our structure provides a foundation for developing models Of remodeler function, including mechanisms of coupling between ARPs and the ATPase translocation activity.