Diversity and Evolution of Bacterial Twin Arginine Translocase Protein, TatC, Reveals a Protein Secretion System That Is Evolving to Fit Its Environmental Niche

BackgroundThe twin-arginine translocation (Tat) protein export system enables the transport of fully folded proteins across a membrane. This system is composed of two integral membrane proteins belonging to TatA and TatC protein families and in some systems a third component, TatB, a homolog of TatA. TatC participates in substrate protein recognition through its interaction with a twin arginine leader peptide sequence.Methodology/Principal FindingsThe aim of this study was to explore TatC diversity, evolution and sequence conservation in bacteria to identify how TatC is evolving and diversifying in various bacterial phyla. Surveying bacterial genomes revealed that 77% of all species possess one or more tatC loci and half of these classes possessed only tatC and tatA genes. Phylogenetic analysis of diverse TatC homologues showed that they were primarily inherited but identified a small subset of taxonomically unrelated bacteria that exhibited evidence supporting lateral gene transfer within an ecological niche. Examination of bacilli tatCd/tatCy isoform operons identified a number of known and potentially new Tat substrate genes based on their frequent association to tatC loci. Evolutionary analysis of these Bacilli isoforms determined that TatCy was the progenitor of TatCd. A bacterial TatC consensus sequence was determined and highlighted conserved and variable regions within a three dimensional model of the Escherichia coli TatC protein. Comparative analysis between the TatC consensus sequence and Bacilli TatCd/y isoform consensus sequences revealed unique sites that may contribute to isoform substrate specificity or make TatA specific contacts. Synonymous to non-synonymous nucleotide substitution analyses of bacterial tatC homologues determined that tatC sequence variation differs dramatically between various classes and suggests TatC specialization in these species.Conclusions/SignificanceTatC proteins appear to be diversifying within particular bacterial classes and its specialization may be driven by the substrates it transports and the environment of its host.背景 双精氨酸易位（twin-arginine translocation, Tat）蛋白分泌系统可介导完全折叠的蛋白质跨膜转运。该系统由两类分别属于TatA和TatC蛋白家族的整合膜蛋白（integral membrane proteins）组成，部分系统还包含第三种组分TatB——TatA的同源物（homolog）。TatC可通过与双精氨酸引导肽（leader peptide）序列相互作用，参与底物蛋白的识别过程。 方法/主要发现 本研究旨在探究细菌中TatC的多样性、演化过程与序列保守性，以明确TatC在不同细菌门类中的演化与分化模式。对细菌基因组的系统性调研显示，77%的细菌物种拥有一个或多个tatC基因座，其中半数类群仅携带tatC与tatA基因。对多种TatC同源物的系统发育分析（phylogenetic analysis）表明，其遗传模式主要为垂直传递，但同时也鉴定出一小类分类学上无亲缘关系的细菌类群，其基因组存在生态位内水平基因转移（lateral gene transfer）的证据。对芽孢杆菌tatCd/tatCy亚型（isoform）操纵子（operon）的分析表明，基于其与tatC基因座的高频关联，可发现一批已知及潜在的新型Tat底物基因。对这些芽孢杆菌亚型的演化分析证实，TatCy是TatCd的祖先序列。我们还确定了细菌TatC的保守共有序列（consensus sequence），并在大肠杆菌TatC蛋白的三维结构模型中标注出保守区域与可变区域。对比TatC保守共有序列与芽孢杆菌TatCd/y亚型保守共有序列的分析结果，发现了若干独特位点，这些位点可能参与调控亚型底物特异性或介导与TatA的特异性相互作用。对细菌tatC同源物的同义与非同义核苷酸替换（synonymous to non-synonymous nucleotide substitution）分析表明，不同细菌类群的tatC序列变异程度差异显著，提示这些物种中的TatC发生了功能特化。 结论与意义 TatC蛋白似乎在特定细菌类群中发生着分化，其功能特化可能由其所转运的底物以及宿主所处的环境所驱动。