The crystal structure of the conserved GTPase of SRP54 from the archaeon Acidianus ambivalens and its comparison with related structures suggests a model for the SRP-SRP receptor complex
The crystal structure of the conserved GTPase of SRP54 from the archaeon Acidianus ambivalens and its comparison with related structures suggests a model for the SRP-SRP receptor complex
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DOI：
10.1016/s0969-2126(00)00131-3
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发表时间：
2000-05-15
期刊：
影响因子：
5.7
通讯作者：
Sinning, I
中科院分区：
文献类型：
--
作者：
Montoya, G;Kaat, KT;Sinning, I
背景资料：真核生物中蛋白质靶向内质网，原核生物中蛋白质靶向细胞膜是由信号识别颗粒（SRP）及其受体（SR）介导的。两者都含有信号肽结合蛋白（SRP 54和Ffh）和SR蛋白（SR α和FtsY）中的保守GTs结构域。这些GTP酶参与蛋白质靶向的调节。到目前为止，大多数研究都集中在哺乳动物和细菌的SRP机制，留下的SRP系统的古菌不太好understood.Results：我们报告的晶体结构的保守的GTtheta（NG-Ffh）从嗜热古菌Acidianus ambivalens在2.0埃分辨率和的Thr 112-->Ala突变体，这是在GTP水解无活性。这是第一个结构的SRP组件从古菌，并允许详细比较与相关结构从大肠杆菌和嗜热细菌。特别是，观察到核苷酸结合的保守共有区域和子域界面的差异，这提供了有关GTPase调节的信息。这些相互作用使我们能够提出一个共同的信号传导机制的SRP-SR system.Conclusions：SRP-GTPases的整体结构是很好的细菌和古细菌之间的保守性，这表明强烈的相似性，在调节的SRP靶向通路。令人惊讶的是，结构比较确定了同源二聚体ATP结合蛋白作为最近的亲戚。提出了SRP-SR相互作用的异二聚体模型。
Background: Protein targeting to the endoplasmic reticulum in eukaryotes and to the cell membrane in prokaryotes is mediated by the signal recognition particle (SRP) and its receptor (SR). Both contain conserved GTPase domains in the signal-peptide-binding proteins (SRP54 and Ffh) and the SR proteins (SR alpha and FtsY). These GTPases are involved in the regulation of protein targeting. Most studies so far have focussed on the SRP machinery of mammals and bacteria, leaving the SRP system of archaea less well understood.Results: We report the crystal structure of the conserved GTPase (NG-Ffh) from the thermophilic archaeon Acidianus ambivalens at 2.0 Angstrom resolution and of the Thr112-->Ala mutant, which is inactive in GTP hydrolysis. This is the first structure of an SRP component from an archaeon and allows for a detailed comparison with related structures from Escherichia coli and thermophilic bacteria. In particular, differences in the conserved consensus regions for nucleotide binding and the subdomain interfaces are observed, which provide information about the regulation of the GTPase. These interactions allow us to propose a common signalling mechanism for the SRP-SR system.Conclusions: The overall structure of SRP-GTPases is well conserved between bacteria and archaea, which indicates strong similarities in the regulation of the SRP-targeting pathway. Surprisingly, structure comparisons identified a homodimeric ATP-binding protein as the closest relative. A heterodimer model for the SRP-SR interaction is presented.