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Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains

机译：古代细胞内小分子结合域的调控潜力，系统分布和进化

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摘要

Central cellular functions such as metabolism, solute transport and signal transduction are regulated, in part, via binding of small. molecules by specialized domains. Using sensitive methods for sequence profile analysis and protein structure comparison, we exhaustively surveyed the protein sets from completely sequenced genomes for all occurrences of 21 intracellular small-molecule-binding domains (SMBDs) that are represented in at least two of the three major divisions of life (bacteria, archaea and eukaryotes). These included previously characterized domains such as PAS, GAF, ACT and ferredoxins, as well as three newly predicted SMBDs, namely the 4-vinyl reductase (4VR) domain, the NIFX domain and the S-histidines (3H) domain. Although there are only a limited number of different superfamilies of these ancient SMBDs, they are present in numerous distinct proteins combined with various enzymatic, transport and signal-transducing domains. Most of the SMBDs show considerable evolutionary mobility and are involved in the generation of many lineage-specific domain architectures. Frequent re-invention of analogous architectures involving functionally related, but not homologous, domains was detected, such as, fusion of different SMBDs to several types of DNA-binding domains to form diverse transcription regulators in prokaryotes and eukaryotes. This is suggestive of similar selective forces affecting the diverse SMBDs and resulting in the formation of multidomain proteins that fit a limited number of functional stereotypes. Using the "guilt by association approach", the identification of SMBDs allowed prediction of functions and mode of regulation for a variety of previously uncharacterized proteins. (C) 2001 Academic Press. [References: 79]
机译：诸如新陈代谢，溶质转运和信号转导等中央细胞功能部分地通过小分子的结合来调节。分子通过专门领域。使用敏感的方法进行序列概况分析和蛋白质结构比较，我们详尽地调查了完全测序的基因组中所有出现的21个细胞内小分子结合域（SMBD）的蛋白质集，这些结构域在以下三个主要区域的至少两个中代表生活（细菌，古细菌和真核生物）。这些包括先前表征的结构域，例如PAS，GAF，ACT和铁氧还蛋白，以及三个新预测的SMBD，即4-乙烯基还原酶（4VR）结构域，NIFX结构域和S-组氨酸（3H）结构域。尽管这些古老的SMBD仅有数量有限的不同超家族，但它们存在于众多不同的蛋白质中，并结合了各种酶促，转运和信号传导域。大多数SMBD显示出相当大的进化移动性，并参与了许多沿袭特定域架构的生成。检测到频繁重复发明涉及功能相关但非同源结构域的类似结构，例如将不同的SMBD与几种类型的DNA结合结构域融合，从而在原核生物和真核生物中形成多种转录调节因子。这表明影响不同SMBD的相似选择力，并导致形成适合有限数量的功能性刻板印象的多域蛋白。使用“内gui关联法”，SMBD的鉴定可以预测多种以前未表征的蛋白质的功能和调控方式。 （C）2001学术出版社。 [参考：79]

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