Comparative genomics of cyclic-di-GMP signalling in bacteria: post-translational regulation and catalytic activity.
Comparative genomics of cyclic-di-GMP signalling in bacteria: post-translational regulation and catalytic activity.
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DOI：
10.1093/nar/gkq382
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发表时间：
2010-10
影响因子：
14.9
通讯作者：
Luscombe NM
中科院分区：
文献类型：
--
作者：
Seshasayee AS;Fraser GM;Luscombe NM
Cyclic-di-GMP是一种细菌第二信使，控制着运动状态和固着状态之间的转换。它由含有酶促GGDEF结构域的蛋白质合成，并由EAL结构域降解。许多细菌基因组编码含有这些结构域的蛋白质的几个拷贝，提出了关于平行的c-di-GMP信号传导系统的活动如何被分离以避免潜在有害的串扰的问题。此外，许多“杂合”蛋白含有GGDEF和EAL结构域;这两种明显相反的酶活性之间的关系被称为“生物化学难题”。在这里，我们提出了一个计算分析11 248 GGDEF-和EAL-含有蛋白质的867原核基因组，以解决这两个悬而未决的问题。这些蛋白质中有一半以上含有细胞表面定位的信号，大多数容纳信号感应伴侣结构域;这些表明翻译后调节的广泛流行，可能会分离共表达的蛋白质的活性。通过研究GGDEF和EAL催化位点中氨基酸残基的保守性，我们发现主要有两种类型的杂交蛋白。在第一个，这两个网站是完整的，一个额外的监管伙伴结构域，目前在大多数这些蛋白质，可能会决定两个酶活性之间的平衡。在第二种类型中，只有EAL催化位点是完整的，这些-不像EAL-只有蛋白质-通常包含一个信号感应伴侣结构域，这表明不同的模式下的EAL活性的调节不同的序列上下文。最后，我们讨论了蛋白质的作用，失去了GGDEF和EAL催化位点作为潜在的c-di-GMP结合效应。我们的研究结果将作为一个基因组框架，用于解释正在进行的这些蛋白质的分子研究。
Cyclic-di-GMP is a bacterial second messenger that controls the switch between motile and sessile states. It is synthesized by proteins containing the enzymatic GGDEF domain and degraded by the EAL domain. Many bacterial genomes encode several copies of proteins containing these domains, raising questions on how the activities of parallel c-di-GMP signalling systems are segregated to avoid potentially deleterious cross-talk. Moreover, many ‘hybrid’ proteins contain both GGDEF and EAL domains; the relationship between the two apparently opposing enzymatic activities has been termed a ‘biochemical conundrum’. Here, we present a computational analysis of 11 248 GGDEF- and EAL-containing proteins in 867 prokaryotic genomes to address these two outstanding questions. Over half of these proteins contain a signal for cell-surface localization, and a majority accommodate a signal-sensing partner domain; these indicate widespread prevalence of post-translational regulation that may segregate the activities of proteins that are co-expressed. By examining the conservation of amino acid residues in the GGDEF and EAL catalytic sites, we show that there are predominantly two types of hybrid proteins. In the first, both sites are intact; an additional regulatory partner domain, present in most of these proteins, might determine the balance between the two enzymatic activities. In the second type, only the EAL catalytic site is intact; these—unlike EAL-only proteins—generally contain a signal-sensing partner domain, suggesting distinct modes of regulation for EAL activity under different sequence contexts. Finally, we discuss the role of proteins that have lost GGDEF and EAL catalytic sites as potential c-di-GMP-binding effectors. Our findings will serve as a genomic framework for interpreting ongoing molecular investigations of these proteins.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
5.8
作者：
Amikam, D;Galperin, MY
通讯作者：
Galperin, MY
影响因子：
2.1
作者：
Aravind, L;Ponting, CP
通讯作者：
Ponting, CP
影响因子：
3.2
作者：
Holland, Linda M.;O'Donnell, Sinead T.;O'Gara, James P.
通讯作者：
O'Gara, James P.
影响因子：
3.2
作者：
AMIKAM, D;BENZIMAN, M
通讯作者：
BENZIMAN, M