The structure of an Iws1/Spt6 complex reveals an interaction domain conserved in TFIIS, Elongin A and Med26
The structure of an Iws1/Spt6 complex reveals an interaction domain conserved in TFIIS, Elongin A and Med26
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DOI：
10.1038/emboj.2010.272
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发表时间：
2010-12-01
期刊：
影响因子：
11.4
通讯作者：
Romier, Christophe
中科院分区：
文献类型：
--
作者：
Diebold, Marie-Laure;Koch, Michael;Romier, Christophe
延伸因子Spt 6与Iws 1的结合为偶联真核生物mRNA合成、染色质重塑和mRNA输出提供了有效手段。我们发现，Spt 6（Spt 6 N）的N-末端区域负责与Iws 1的相互作用。兔脑炎原虫Iws 1和Iws 1/Spt 6 N复合体的晶体结构揭示了Iws 1中两个保守的结合亚结构域。第一个亚结构域（一个HEAT重复序列; HEAT亚结构域）是一个假定的磷蛋白结合位点，最有可能参与Iws 1的Spt 6独立功能。第二个子域（两个ARM重复; ARM子域）特异性识别Spt 6的二分N-末端区域。改变Spt 6的该区域的突变在体内引起严重的表型。重要的是，Iws 1的ARM亚结构域在几种转录因子中是保守的，包括TFIIS，Elongin A和Med 26。我们发现，在酵母TFIIS的同源区域，使这个因素与佐贺和中介亚基Spt 8和Med 13相互作用，这表明TFIIS招聘在启动子的分子基础。总之，我们的研究结果提供了新的结构信息Iws 1/Spt 6复合物，并揭示了一个新的相互作用域用于形成转录网络。The EMBO Journal（2010）29，3979-3991. doi：10.1038/doj.2010.272; 2010年11月5日在线发布
Binding of elongation factor Spt6 to Iws1 provides an effective means for coupling eukaryotic mRNA synthesis, chromatin remodelling and mRNA export. We show that an N-terminal region of Spt6 (Spt6N) is responsible for interaction with Iws1. The crystallographic structures of Encephalitozoon cuniculi Iws1 and the Iws1/Spt6N complex reveal two conserved binding subdomains in Iws1. The first subdomain (one HEAT repeat; HEAT subdomain) is a putative phosphoprotein-binding site most likely involved in an Spt6-independent function of Iws1. The second subdomain (two ARM repeats; ARM subdomain) specifically recognizes a bipartite N-terminal region of Spt6. Mutations that alter this region of Spt6 cause severe phenotypes in vivo. Importantly, the ARM subdomain of Iws1 is conserved in several transcription factors, including TFIIS, Elongin A and Med26. We show that the homologous region in yeast TFIIS enables this factor to interact with SAGA and the Mediator subunits Spt8 and Med13, suggesting the molecular basis for TFIIS recruitment at promoters. Taken together, our results provide new structural information about the Iws1/Spt6 complex and reveal a novel interaction domain used for the formation of transcription networks. The EMBO Journal (2010) 29, 3979-3991. doi:10.1038/emboj.2010.272; Published online 5 November 2010