Structural evidence for a common intermediate in small G protein-GEF reactions.
Structural evidence for a common intermediate in small G protein-GEF reactions.
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DOI：
10.1016/j.molcel.2006.11.023
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发表时间：
2007-01
期刊：
影响因子：
16
通讯作者：
Christoph Thomas;Inka Fricke;A. Scrima;A. Berken;A. Wittinghofer
中科院分区：
文献类型：
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作者：
Christoph Thomas;Inka Fricke;A. Scrima;A. Berken;A. Wittinghofer
植物Rho蛋白（Rop）属于小G蛋白超家族，是植物信号转导的重要调节因子。为了被激活，Rop蛋白需要将GDP交换为GTP，这是一个由鸟嘌呤核苷酸交换因子（GEF）催化的内在缓慢过程。RopGEFs与动物RhoGEFs没有同源性，催化机制仍然难以捉摸。GEF催化的核苷酸交换通过瞬时三元和稳定二元复合物进行。虽然一些结构研究已经分析了二元无核苷酸G蛋白-GEF复合物，但对三元复合物知之甚少。在这里，我们报告的X-射线结构的催化PRONE结构域的RopGEF8从拟南芥，无论是单独的和在一个三元复合物与Rop4和GDP。后一种复合物是以前从未直接观察到的交换反应的短暂中间体，其特征表明催化核苷酸交换的常见机制一般适用于小G蛋白。
Rho of plants (Rop) proteins belong to the superfamily of small GTP-binding (G) proteins and are vital regulators of signal transduction in plants. In order to become activated, Rop proteins need to exchange GDP for GTP, an intrinsically slow process catalyzed by guanine nucleotide exchange factors (GEFs). RopGEFs show no homology to animal RhoGEFs, and the catalytic mechanism remains elusive. GEF-catalysed nucleotide exchange proceeds via transient ternary and stable binary complexes. While a number of structural studies have analyzed binary nucleotide-free G protein-GEF complexes, very little is known about the ternary complexes. Here we report the X-ray structure of the catalytic PRONE domain of RopGEF8 fromArabidopsis thaliana, both alone and in a ternary complex with Rop4 and GDP. The features of the latter complex, a transient intermediate of the exchange reaction never directly observed before, suggest a common mechanism of catalyzed nucleotide exchange applicable to small G proteins in general.