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首页> 外文期刊>EMBO Journal >Structure of the Roc-COR domain tandem of C-tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase
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Structure of the Roc-COR domain tandem of C-tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase

机译：Roc-COR域串联的结构C-tepidum,原核的同系物的人类LRRK2帕金森激酶

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摘要

Ras of complex proteins (Roc) belongs to the superfamily of Ras-related small G-proteins that always occurs in tandem with the C-terminal of Roc (COR) domain. This Roc-COR tandem is found in the bacterial and eukaryotic world. Its most prominent member is the leucine-rich repeat kinase LRRK2, which is mutated and activated in Parkinson patients. Here, we investigated biochemically and structurally the Roco protein from Chlorobium tepidum. We show that Roc is highly homologous to Ras, whereas the COR domain is a dimerisation device. The juxtaposition of the G-domains and mutational analysis suggest that the Roc GTPase reaction is stimulated and/or regulated by dimerisation in a nucleotide-dependent manner. The region most conserved between bacteria and man is the interface between Roc and COR, where single-point Parkinson mutations of the Roc and COR domains are in close proximity. The analogous mutations in C. tepidum Roc-COR decrease the GTPase reaction rate, most likely due to a modification of the interaction between the Roc and COR domains.
机译：Ras (Roc)属于复杂的蛋白质总科Ras-related小g总是发生在串联的c端中华民国(软木)域。细菌和真核生物的世界。主要成员是富亮氨酸重复体内基因LRRK2激酶,突变和激活帕金森患者。生化和结构Roco的蛋白质从绿硫细菌tepidum。Ras高度同源,而软木域是一个二聚装置。G-domains和突变分析中华民国GTPase反应和/或刺激由二聚作用nucleotide-dependent方式。守恒的细菌和人之间中华民国和软木,单点帕金森突变的中华民国和软木域在近距离。在c . tepidum Roc-COR降低GTPase反应速率,最有可能由于修改中华民国之间的交互和心脏域。

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