The crystal structure of the Split End protein SHARP adds a new layer of complexity to proteins containing RNA recognition motifs.
The crystal structure of the Split End protein SHARP adds a new layer of complexity to proteins containing RNA recognition motifs.
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DOI：
10.1093/nar/gku277
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发表时间：
2014-06
影响因子：
14.9
通讯作者：
Thore S
中科院分区：
文献类型：
--
作者：
Arieti F;Gabus C;Tambalo M;Huet T;Round A;Thore S
分裂末端（SPEN）蛋白最初于20世纪90年代末在果蝇中发现。从那时起，同源蛋白质已经在从植物到人类的真核生物中被鉴定出来。每个家族成员在蛋白质的N-末端区域包含三个预测的RNA识别基序（RRM）。我们已经确定了人类SPEN同源物中含有这些RRMs的区域的晶体结构-SMRT/HDAC 1相关阻遏蛋白（SHARP），分辨率为2.0 μ m。SHARP是核受体的辅助调节剂。我们证明了三个RRMs中的两个，即RRM 3和RRM 4，通过高度保守的界面相互作用。此外，我们表明，RRM 3-RRM 4块是介导与类固醇受体RNA激活剂（SRA）中发现的H12-H13子结构稳定关联的主要平台，SRA是一种长的非编码RNA，以前被证明在核受体转录调控中起着至关重要的作用。我们确定SHARP与SRA的关联依赖于单链和双链RNA序列。SHARP-RRM片段的晶体结构，以及相关的RNA结合研究，扩展了RRM结构域的核酸结合特性的库，这为更好地理解SPEN蛋白功能提出了一个新的假设。
The Split Ends (SPEN) protein was originally discovered in Drosophila in the late 1990s. Since then, homologous proteins have been identified in eukaryotic species ranging from plants to humans. Every family member contains three predicted RNA recognition motifs (RRMs) in the N-terminal region of the protein. We have determined the crystal structure of the region of the human SPEN homolog that contains these RRMs—the SMRT/HDAC1 Associated Repressor Protein (SHARP), at 2.0 Å resolution. SHARP is a co-regulator of the nuclear receptors. We demonstrate that two of the three RRMs, namely RRM3 and RRM4, interact via a highly conserved interface. Furthermore, we show that the RRM3–RRM4 block is the main platform mediating the stable association with the H12–H13 substructure found in the steroid receptor RNA activator (SRA), a long, non-coding RNA previously shown to play a crucial role in nuclear receptor transcriptional regulation. We determine that SHARP association with SRA relies on both single- and double-stranded RNA sequences. The crystal structure of the SHARP–RRM fragment, together with the associated RNA-binding studies, extend the repertoire of nucleic acid binding properties of RRM domains suggesting a new hypothesis for a better understanding of SPEN protein functions.
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影响因子：
64.5
作者：
Malovannaya A;Lanz RB;Jung SY;Bulynko Y;Le NT;Chan DW;Ding C;Shi Y;Yucer N;Krenciute G;Kim BJ;Li C;Chen R;Li W;Wang Y;O'Malley BW;Qin J
通讯作者：
Qin J
影响因子：
14.9
作者：
Cook KB;Kazan H;Zuberi K;Morris Q;Hughes TR
通讯作者：
Hughes TR
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：
6.8
作者：
Daubner, Gerrit M.;Clery, Antoine;Allain, Frederic H-T
通讯作者：
Allain, Frederic H-T
影响因子：
2.9
作者：
Newberry, EP;Latifi, T;Towler, DA
通讯作者：
Towler, DA