Crystal structures of the S. cerevisiae Spt6 core and C-terminal tandem SH2 domain.
Crystal structures of the S. cerevisiae Spt6 core and C-terminal tandem SH2 domain.
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DOI：
10.1016/j.jmb.2011.03.002
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发表时间：
2011-05-13
影响因子：
5.6
通讯作者：
Hill CP
中科院分区：
文献类型：
--
作者：
Close D;Johnson SJ;Sdano MA;McDonald SM;Robinson H;Formosa T;Hill CP
Spt 6是一种重要的真核生物蛋白，在转录延伸、染色质维持和RNA加工中发挥重要作用。Spt 6有三个特征功能。它是一种能够重组核小体的组蛋白伴侣，是转录延伸复合物的中心组分，并且是RNA加工因子募集至延伸RNA聚合酶II（RNAPII）所需的。在这里，我们报告的晶体结构的168 kDa的Spt 6蛋白从酿酒酵母，共同代表基本上所有的有序序列。我们的~900个残基的核心区域的两个结构揭示了一系列推定的核酸和蛋白质-蛋白质相互作用结构域，其折叠成类似于细菌蛋白Tex的细长形式。与细菌转录因子的相似性表明，核心结构域执行核小体独立的活动，并且与Tex一样，我们发现Spt 6结合DNA。然而，与Tex不同，Spt 6 S1结构域对这种活性没有贡献。Spt 6 C-末端区域的晶体结构揭示了由两个紧密相关的SH 2折叠组成的串联SH 2结构域结构。这些SH 2折叠之一是隐蔽的，而另一个共享惊人的结构相似性与后生动物SH 2域，并具有与结合磷酸化底物，包括磷酸酪氨酸的能力相关的结构特征。与磷酸肽，模拟RNAPII CTD的结合研究显示，其他RNAPII CTD结合蛋白的典型亲和力，但没有表明一个特定的相互作用。总的来说，这些发现为理解Spt 6如何在单个多肽链内编码几种不同的功能提供了结构基础。
The conserved and essential eukaryotic protein Spt6 functions in transcription elongation, chromatin maintenance, and RNA processing. Spt6 has three characterized functions. It is a histone chaperone capable of reassembling nucleosomes, a central component of transcription elongation complexes, and is required for recruitment of RNA processing factors to elongating RNA polymerase II (RNAPII). Here, we report crystal structures of the 168 kDa Spt6 protein from Saccharomyces cerevisiae that together represent essentially all of the ordered sequence. Our two structures of the ~900 residue core region reveal a series of putative nucleic acid and protein-protein interaction domains that fold into an elongated form that resembles the bacterial protein Tex. The similarity to a bacterial transcription factor suggests that the core domain performs nucleosome-independent activities, and as with Tex we find that Spt6 binds DNA. Unlike Tex, however, the Spt6 S1 domain does not contribute to this activity. Crystal structures of the Spt6 C-terminal region reveal a tandem SH2 domain structure comprised of two closely associated SH2 folds. One of these SH2 folds is cryptic, while the other shares striking structural similarity with metazoan SH2 domains and possesses structural features associated with the ability to bind phosphorylated substrates including phosphotyrosine. Binding studies with phosphopeptides that mimic the RNAPII CTD revealed affinities typical of other RNAPII CTD-binding proteins but did not indicate a specific interaction. Overall, these findings provide a structural foundation for understanding how Spt6 encodes several distinct functions within a single polypeptide chain.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
64.8
作者：
Andrulis, ED;Werner, J;Lis, JT
通讯作者：
Lis, JT
影响因子：
4.8
作者：
Kaplan, CD;Holland, MJ;Winston, F
通讯作者：
Winston, F
影响因子：
5.6
作者：
Grant, Richard P.;Marshall, Neil J.;Yang, Ji-Chun;Fasken, Milo B.;Kelly, Seth M.;Harrernan, Michelle T.;Neuhaus, David;Corbett, Anita H.;Stewart, Murray
通讯作者：
Stewart, Murray