Anantharaman V, Koonin E V, Aravind L
National Center for Biotechnology Information National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
J Mol Biol. 2001 Apr 13;307(5):1271-92. doi: 10.1006/jmbi.2001.4508.
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 3-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.
诸如新陈代谢、溶质转运和信号转导等核心细胞功能部分是通过小分子与特定结构域的结合来调节的。我们使用敏感的序列谱分析和蛋白质结构比较方法，详尽地调查了来自完全测序基因组的蛋白质组，以查找21种细胞内小分子结合结构域（SMBD）的所有出现情况，这些结构域在生命的三个主要分类（细菌、古细菌和真核生物）中的至少两个分类中都有代表。这些结构域包括先前已表征的结构域，如PAS、GAF、ACT和铁氧化还原蛋白，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3-组氨酸（3H）结构域。尽管这些古老的SMBD只有有限数量的不同超家族，但它们存在于众多不同的蛋白质中，并与各种酶、转运和信号转导结构域结合。大多数SMBD显示出相当大的进化灵活性，并参与了许多谱系特异性结构域架构的产生。我们检测到涉及功能相关但不同源的结构域频繁重新发明类似的架构，例如，在原核生物和真核生物中，不同的SMBD与几种类型的DNA结合结构域融合，形成多种转录调节因子。这表明存在类似的选择力影响着不同的SMBD，并导致形成符合有限数量功能模式的多结构域蛋白质。使用“关联有罪方法”，SMBD的鉴定有助于预测多种先前未表征蛋白质的功能和调节模式。
