Structural basis for recognition of diverse transcriptional repressors by the TOPLESS family of corepressors.
Structural basis for recognition of diverse transcriptional repressors by the TOPLESS family of corepressors.
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DOI：
10.1126/sciadv.1500107
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发表时间：
2015-07
期刊：
影响因子：
13.6
通讯作者：
Melcher K
中科院分区：
文献类型：
--
作者：
Ke J;Ma H;Gu X;Thelen A;Brunzelle JS;Li J;Xu HE;Melcher K
植物中的Groucho相关辅阻遏物通过一种新的肽识别折叠结合在许多阻遏物中发现的肽基序。TOPLESS（TPL）和TOPLESS相关（TPR）蛋白包括与酵母、昆虫和哺乳动物中的Tup 1、Groucho和TLE（transformin-like enhancer of split）辅阻遏物相关的植物转录辅阻遏物的保守家族。在植物中，TPL/TPR辅阻遏物通过与在不同转录阻遏物中发现的小乙烯反应因子相关的两亲性阻遏（ERFs）基序相互作用来调节发育、胁迫反应和激素信号传导。TPL/TPR蛋白如何与TPL/TPR基序相互作用尚不清楚。我们确认的氨基末端结构域的TPL家族的辅阻遏物，我们称之为TOPLESS域（TPD），作为peptide基序结合域。为了理解这种相互作用的结构基础，我们确定了在apo（apo蛋白）状态下以及与拟南芥NINJA（JAZ的新型相互作用物），IAA 1（生长素响应蛋白1）和IAA 10（茉莉酸和生长素信号传导中涉及的关键转录抑制因子）的复合物中水稻（Os）TPR 2的TPD的晶体结构。OsTPR 2 TPD采用了一种新的九螺旋折叠，随后是一个锌指，它们排列成盘状四聚体。三种不同复合物中的疏水基序采用相似的延伸构象，疏水残基适合每个OsTPR 2单体的相同表面凹槽。序列比对和基于结构的诱变表明，这种模式的辅阻遏物结合是高度保守的一个大的转录阻遏物，从而提供了一个一般的机制，由TPL家族的辅阻遏物介导的基因阻遏。
Groucho-related corepressors in plants bind a peptide motif found in numerous repressors through a novel peptide recognition fold. TOPLESS (TPL) and TOPLESS-related (TPR) proteins comprise a conserved family of plant transcriptional corepressors that are related to Tup1, Groucho, and TLE (transducin-like enhancer of split) corepressors in yeast, insects, and mammals. In plants, TPL/TPR corepressors regulate development, stress responses, and hormone signaling through interaction with small ethylene response factor–associated amphiphilic repression (EAR) motifs found in diverse transcriptional repressors. How EAR motifs can interact with TPL/TPR proteins is unknown. We confirm the amino-terminal domain of the TPL family of corepressors, which we term TOPLESS domain (TPD), as the EAR motif–binding domain. To understand the structural basis of this interaction, we determined the crystal structures of the TPD of rice (Os) TPR2 in apo (apo protein) state and in complexes with the EAR motifs from Arabidopsis NINJA (novel interactor of JAZ), IAA1 (auxin-responsive protein 1), and IAA10, key transcriptional repressors involved in jasmonate and auxin signaling. The OsTPR2 TPD adopts a new fold of nine helices, followed by a zinc finger, which are arranged into a disc-like tetramer. The EAR motifs in the three different complexes adopt a similar extended conformation with the hydrophobic residues fitting into the same surface groove of each OsTPR2 monomer. Sequence alignments and structure-based mutagenesis indicate that this mode of corepressor binding is highly conserved in a large set of transcriptional repressors, thus providing a general mechanism for gene repression mediated by the TPL family of corepressors.