The Evolution of Guanylyl Cyclases as Multidomain Proteins: Conserved Features of Kinase-Cyclase Domain Fusions
The Evolution of Guanylyl Cyclases as Multidomain Proteins: Conserved Features of Kinase-Cyclase Domain Fusions
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DOI：
10.1007/s00239-009-9242-5
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
Visweswariah, Sandhya S.
中科院分区：
文献类型：
--
作者：
Biswas, Kabir Hassan;Shenoy, Avinash R.;Visweswariah, Sandhya S.
鸟苷酸环化酶 (GC) 是产生环 GMP 并调节许多生物体不同生理和发育过程的酶。 GC 与 III 类腺苷酸环化酶 (AC) 具有序列相似性，并且以膜结合受体 GC 或胞质可溶性 GC 的形式存在。我们试图通过大规模生物信息学分析来确定 GC 的进化，并在许多真核生物的基因组中发现了 GC 基因的多个谱系特异性扩展。此外，在原核生物中发现了一些类似GC的蛋白质，它们与许多不同的结构域融合，表明核苷酸环化酶活性的变构调节。真核受体 GC 与激酶同源结构域 (KHD) 相关，这些蛋白质的系统发育分析表明 KHD 和相关环化酶结构域的共同进化，以及 KHD 和相关环化酶结构域之间的连接区域的序列和大小的保守性。最后，我们还报告了含有与环化酶结构域相关的推定活性激酶结构域的模拟病毒蛋白的存在，这可能表明参与信号转导的这两个重要结构域的融合的早期进化。
Guanylyl cyclases (GCs) are enzymes that generate cyclic GMP and regulate different physiologic and developmental processes in a number of organisms. GCs possess sequence similarity to class III adenylyl cyclases (ACs) and are present as either membrane-bound receptor GCs or cytosolic soluble GCs. We sought to determine the evolution of GCs using a large-scale bioinformatic analysis and found multiple lineage-specific expansions of GC genes in the genomes of many eukaryotes. Moreover, a few GC-like proteins were identified in prokaryotes, which come fused to a number of different domains, suggesting allosteric regulation of nucleotide cyclase activity. Eukaryotic receptor GCs are associated with a kinase homology domain (KHD), and phylogenetic analysis of these proteins suggest coevolution of the KHD and the associated cyclase domain as well as a conservation of the sequence and the size of the linker region between the KHD and the associated cyclase domain. Finally, we also report the existence of mimiviral proteins that contain putative active kinase domains associated with a cyclase domain, which could suggest early evolution of the fusion of these two important domains involved in signal transduction.