The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life.

The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life.
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DOI:
10.1371/journal.pone.0023479
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Hauryliuk V
Hauryliuk V
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Atkinson GC;Tenson T;Hauryliuk V

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RelA/Spot Homologue(RSH)蛋白因其序列与大肠杆菌的RelA和Spot酶相似而得名,它由一个超家族的酶组成,该超家族合成和/或水解丙酮ppGpp,后者是“严格”反应的激活剂和细胞代谢的调节因子。在不同的细菌和植物叶绿体中发现了经典的具有ppGpp水解酶、合成酶、TGS和ACT结构域的长的RSHS Rel、RelA和Spot,而在不同的细菌和动物中也分别发现了专门的单结构域ppGpp合成和水解RSHS。然而,在命名方面存在相当大的混乱,以前还没有进行全面的系统发育和序列分析来在基因组规模上对RSHS进行分类。我们对生命之树上的1000多个基因组进行了高通量的敏感序列搜索,结合系统发育分析,巩固了先前在不同生物体中对不同RSH的特殊识别,并为该领域提供了亟需的统一术语。我们将RSHS分为30个亚组,包括三个亚组:长RSHS、小丙酮合成酶(SASS)和小丙酮水解酶(SAH)。19个以前未知的RSH亚群的成员现在可以进行实验研究,包括以前在古生菌中未知的RSH,扩大了对这一生命领域的“严格反应”。我们分析了细菌基因组中RSH蛋白及其结构域的可能组合,并将RSH含量与各种生物的RSH敲除数据进行比较,以确定RSH结合的规则。通过对长RHS和小RHS的序列比较分析,我们发现暴露于长RHS的保守区域仅限于我们提出的参与传递调控信号的区域。这样的信号可以通过NTD到CTD的分子内相互作用或分子间相互作用在单个RSH分子之间或在长RSHS和其他结合伙伴(如核糖体)之间传递。
RelA/SpoT Homologue (RSH) proteins, named for their sequence similarity to the RelA and SpoT enzymes of Escherichia coli, comprise a superfamily of enzymes that synthesize and/or hydrolyze the alarmone ppGpp, activator of the “stringent” response and regulator of cellular metabolism. The classical “long” RSHs Rel, RelA and SpoT with the ppGpp hydrolase, synthetase, TGS and ACT domain architecture have been found across diverse bacteria and plant chloroplasts, while dedicated single domain ppGpp-synthesizing and -hydrolyzing RSHs have also been discovered in disparate bacteria and animals respectively. However, there is considerable confusion in terms of nomenclature and no comprehensive phylogenetic and sequence analyses have previously been carried out to classify RSHs on a genomic scale. We have performed high-throughput sensitive sequence searching of over 1000 genomes from across the tree of life, in combination with phylogenetic analyses to consolidate previous ad hoc identification of diverse RSHs in different organisms and provide a much-needed unifying terminology for the field. We classify RSHs into 30 subgroups comprising three groups: long RSHs, small alarmone synthetases (SASs), and small alarmone hydrolases (SAHs). Members of nineteen previously unidentified RSH subgroups can now be studied experimentally, including previously unknown RSHs in archaea, expanding the “stringent response” to this domain of life. We have analyzed possible combinations of RSH proteins and their domains in bacterial genomes and compared RSH content with available RSH knock-out data for various organisms to determine the rules of combining RSHs. Through comparative sequence analysis of long and small RSHs, we find exposed sites limited in conservation to the long RSHs that we propose are involved in transmitting regulatory signals. Such signals may be transmitted via NTD to CTD intra-molecular interactions, or inter-molecular interactions either among individual RSH molecules or among long RSHs and other binding partners such as the ribosome.
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