The neural repressor NRSF/REST binds the PAH1 domain of the Sin3 corepressor by using its distinct short hydrophobic helix
The neural repressor NRSF/REST binds the PAH1 domain of the Sin3 corepressor by using its distinct short hydrophobic helix
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DOI：
10.1016/j.jmb.2005.10.008
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发表时间：
2005-12-09
影响因子：
5.6
通讯作者：
Nishimura, Y
中科院分区：
文献类型：
--
作者：
Nomura, M;Uda-Tochio, H;Nishimura, Y
在非神经元细胞和神经元祖细胞中，许多神经元特异性基因被神经限制性沉默因子（NRSF）/阻遏物元件1沉默转录因子（REST）抑制，其是必需的四个成对的两亲性螺旋（PAH）结构域，PAH 1、PAH 2、PAH 3和独立地。到目前为止，只有PAH 2结构域复合物的三级结构，当绑定到Sin 3相互作用域的Mad 1和HBP 1，已被确定。在这里，我们揭示了NRSF/REST的N-末端阻遏结构域结合到mSin 3B的PAH 1结构域，并确定与NRSF/REST最小阻遏结构域相关的PAH 1结构域的结构。与PAH 2结构相比，PAH 1具有相当球状的四螺旋束结构，具有半有序的C-末端尾部。与Mad 1或HBP 1结合到PAH 2的两亲性α-螺旋相反，NRSF/REST的短疏水性α-螺旋被捕获在PAH 1的裂缝中。NCoR是一种核激素受体辅抑制子，已发现其C末端区域与PAH 1结构域的结合亲和力低于NRSF/REST，该区域含有比NRSF/REST螺旋更少的疏水性氨基酸残基。为了与阻遏物强结合，PAH 1似乎需要阻遏物内主要由疏水氨基酸残基组成的短α-螺旋。Sin 3的四个PAH结构域中的每一个似乎都与特定阻遏物的特征螺旋相互作用; PAH 1需要一个主要是疏水性的螺旋，PAH 2需要每个靶阻遏物中的两亲性螺旋。(c)2005爱思唯尔有限公司保留所有权利。
In non-neuronal cells and neuronal progenitors, many neuron-specific genes are repressed by a neural restrictive silencer factor (NRSF)/repressor element 1 silencing transcription factor (REST), which is an essential four paired amphipathic helix (PAH) domains, PAH1, PAH2, PAH3 and independently. So far, only the tertiary structures of PAH2 domain complexes, when bound to the Sin3-interacting domains of Mad1 and HBP1, have been determined. Here, we reveal that the N-terminal repressor domain of NRSF/REST binds to the PAH1 domain of mSin3B, and determine the structure of the PAH1 domain associated with the NRSF/REST minimal repressor domain. Compared to the PAH2 structure, PAH1 holds a rather globular four-helix bundle structure with a semiordered C-terminal tail. In contrast to the amphipathic alpha-helix of Mad1 or HBP1 bound to PAH2, the short hydrophobic alpha-helix of NRSF/REST is captured in the cleft of PAH1. A nuclear hormone receptor corepressor, NCoR has been found to bind to the PAH1 domain with a lower affinity than NRSF/REST by using its C-terminal region, which contains fewer hydrophobic amino acid residues than the NRSF/REST helix. For strong binding to a repressor, PAH1 seems to require a short alpha-helix consisting of mostly hydrophobic amino acid residues within the repressor. Each of the four PAH domains of Sin3 seems to interact with a characteristic helix of a specific repressor; PAH1 needs a mostly hydrophobic helix and PAH2 needs an amphipathic helix in each target repressor. (c) 2005 Elsevier Ltd. All rights reserved.