p190RhoGAP proteins contain pseudoGTPase domains.

p190RhoGAP proteins contain pseudoGTPase domains.
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DOI:
10.1038/s41467-017-00483-x
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发表时间:
2017-09-11
影响因子:
16.6
通讯作者:
Boggon TJ
Boggon TJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Stiegler AL;Boggon TJ

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两种p190 RhoGAP蛋白,p190 RhoGAP-A和-B,是Rho GT3信号传导的关键调节剂,并且对于肌动蛋白细胞骨架结构和收缩性是必需的。在这里,我们报告发现两个进化上保守的GTP酶样结构域位于“中间域”,以前被认为是非结构化的。这些结构域的缺失降低了RhoGAP活性。晶体结构、MANT-GTPγS结合、热变性、生物化学测定和序列同源性分析都强烈支持核苷酸结合活性的缺陷。因此,p190 RhoGAP蛋白的分析表明存在两个以前未鉴定的结构域,它们代表了一组新兴的假酶,即假GTP酶。越来越多的“假酶”在信号转导过程中的调节作用,但没有催化活性正在确定。在这里,作者确定了p190 RhoGAP中的两个pseudoGTdR结构域,对它们进行了生化和结构表征,并表明它们影响RhoGAP活性。
The two p190RhoGAP proteins, p190RhoGAP-A and -B, are key regulators of Rho GTPase signaling and are essential for actin cytoskeletal structure and contractility. Here we report the discovery of two evolutionarily conserved GTPase-like domains located in the ‘middle domain’, previously thought to be unstructured. Deletion of these domains reduces RhoGAP activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays and sequence homology analysis all strongly support defects in nucleotide-binding activity. Analysis of p190RhoGAP proteins therefore indicates the presence of two previously unidentified domains which represent an emerging group of pseudoenzymes, the pseudoGTPases. A growing number of ‘pseudoenzymes’ with a regulatory role in signal transduction processes but without catalytic activity are being identified. Here, the authors identify two pseudoGTPase domains in p190RhoGAP, characterize them biochemically and structurally and show that they influence RhoGAP activity.
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