Rbg1-Tma46 dimer structure reveals new functional domains and their role in polysome recruitment
Rbg1-Tma46 dimer structure reveals new functional domains and their role in polysome recruitment
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DOI：
10.1093/nar/gks867
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发表时间：
2012-11-01
影响因子：
14.9
通讯作者：
Seraphin, Bertrand
中科院分区：
文献类型：
--
作者：
Francis, Sandrea M.;Gas, Maria-Eugenia;Seraphin, Bertrand
发育调节的GTP结合蛋白(DRG)是与DRG家族调节蛋白(DFRP)相关的高度保守的GTP酶。由此产生的复合体最近被证明参与了真核翻译。用X射线衍射法确定了酵母DRG蛋白Rbg1 GTPase与其DFRP伴侣Tma46的C-末端区域的复合体结构。这些数据表明，DRG蛋白是一个多模块因子，带有三个额外的结构域，螺旋-转角-螺旋(HTH)，S5D2L和TGS，与GTPase平台堆积在一起。令人惊讶的是，S5D2L结构域被插入到GTPase序列的中间。相反，Tma46与Rbg1相互作用的区域采用了典型的固有非结构蛋白的延伸构象，并接触GTPase和TGS结构域。功能分析表明，Rbg1的各个结构域以及Tma46调节Rbg1的GTPase活性，并参与这些蛋白质在体内的功能。对不同结构域的分析表明，Rbg1的TGS结构域对该因子在多聚体中的招募是必不可少的，进一步支持了这些保守因子在翻译中的意义。
Developmentally Regulated GTP-binding (DRG) proteins are highly conserved GTPases that associate with DRG Family Regulatory Proteins (DFRP). The resulting complexes have recently been shown to participate in eukaryotic translation. The structure of the Rbg1 GTPase, a yeast DRG protein, in complex with the C-terminal region of its DFRP partner, Tma46, was solved by X-ray diffraction. These data reveal that DRG proteins are multimodular factors with three additional domains, helix-turn-helix (HTH), S5D2L and TGS, packing against the GTPase platform. Surprisingly, the S5D2L domain is inserted in the middle of the GTPase sequence. In contrast, the region of Tma46 interacting with Rbg1 adopts an extended conformation typical of intrinsically unstructured proteins and contacts the GTPase and TGS domains. Functional analyses demonstrate that the various domains of Rbg1, as well as Tma46, modulate the GTPase activity of Rbg1 and contribute to the function of these proteins in vivo. Dissecting the role of the different domains revealed that the Rbg1 TGS domain is essential for the recruitment of this factor in polysomes, supporting further the implication of these conserved factors in translation.