Structural analysis of human RPC32β-RPC62 complex
Structural analysis of human RPC32β-RPC62 complex
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DOI：
10.1016/j.jsb.2015.09.004
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发表时间：
2015-12-01
影响因子：
3
通讯作者：
Fribourg, Sebastien
中科院分区：
文献类型：
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作者：
Boissier, Fanny;Dumay-Odelot, Helene;Fribourg, Sebastien
真核生物RNA聚合酶（Pol）III的转录起始依赖于亚复合物RPC 62/RPC 39/RPC 32。人类基因组中编码RPC 32的两种不同亚型。RPC 32 α的表达受到高度调节，并且仅在干细胞和转化细胞中发现，而RPC 32 β在组织中普遍表达。在这里，我们确定了一个核心相互作用域的RPC 32足以与RPC 62的相互作用。我们提出了RPC 62和RPC 32 β核心结构域的复合物的晶体结构。RPC 32 β与延伸的翼状螺旋1和2以及RPC 62的卷曲螺旋结构域结合，使RPC 32成为RPC 62结构域之间的分子桥梁。与EM数据拟合的RPC 62-RPC 32复合物表明RPC 32通过与最大的Pol III亚基相互作用和通过溶剂暴露的残基而具有双功能作用。RPC 32定位到Pol III中表明Pol III全酶表面的亚基特异性接触对其功能至关重要。(C)2015爱思唯尔公司All rights reserved.
Transcription initiation by eukaryotic RNA polymerase (Pol) III relies on the subcomplex RPC62/RPC39/RPC32. Two distinct isoforms of RPC32 are encoded in the human genome. RPC32 alpha, expression is highly regulated and found only in stem cells and transformed cells, whereas RPC32 beta is ubiquitously expressed in tissues. Here we identify a core-interacting domain of RPC32 sufficient for the interaction with RPC62. We present the crystal structure of a complex of RPC62 and the RPC32 beta core domain. RPC32 beta associates with the extended winged helix 1 and 2 and the coiled coil domain of RPC62 qualifying RPC32 as a molecular bridge in between RPC62 domains. The RPC62-RPC32 complex fit into EM data suggests a bi-functional role for RPC32 through interactions with the largest Pol III subunit and through solvent exposed residues. RPC32 positioning into Pol III suggests that subunit-specific contacts at the surface of the Pol III holoenzyme are critical for its function. (C) 2015 Elsevier Inc. All rights reserved.