Department of Biological Sciences, University of Waikato, Private Bag 3105, Hamilton 3240, New Zealand.
Protein Eng Des Sel. 2011 Jan;24(1-2):33-40. doi: 10.1093/protein/gzq081. Epub 2010 Oct 29.
The PIN-domains are small proteins of ~130 amino acids that are found in bacteria, archaea and eukaryotes and are defined by a group of three strictly conserved acidic amino acids. The conserved three-dimensional structures of the PIN-domains cluster these acidic residues in an enzymatic active site. PIN-domains cleave single-stranded RNA in a sequence-specific, Mg²+- or Mn²+-dependent manner. These ribonucleases are toxic to the cells which express them and to offset this toxicity, they are co-expressed with tight binding protein inhibitors. The genes encoding these two proteins are adjacent in the genome of all prokaryotic organisms where they are found. This sequential arrangement of inhibitor-RNAse genes conforms to that of the so-called toxin-antitoxin (TA) modules and the PIN-domain TAs have been named VapBC TAs (virulence associated proteins, VapB is the inhibitor which contains a transcription factor domain and VapC is the PIN-domain ribonuclease). The presence of large numbers of vapBC loci in disparate prokaryotes has motivated many researchers to investigate their biochemical and biological functions. For example, the devastating human pathogen Mycobacterium tuberculosis has 45 vapBC loci encoded in its genome whereas its non-pathogenic relative, Mycobacterium smegmatis has just one vapBC operon. On another branch of the prokaryotic tree, the nitrogen-fixing symbiont of legumes, Sinorhizobium meliloti has 21 vapBC loci and at least one of these loci have been implicated in the regulation of growth in the plant nodule. A range of biological functions has been suggested for these operons and this review sets out to survey the PIN-domains and summarise the current knowledge about the vapBC TA systems and their roles in diverse bacteria.
PIN 结构域是一种约 130 个氨基酸的小蛋白，存在于细菌、古菌和真核生物中，由一组三个严格保守的酸性氨基酸定义。PIN 结构域的保守三维结构将这些酸性残基聚类到一个酶活性位点中。PIN 结构域以序列特异性、Mg²+或 Mn²+依赖性方式切割单链 RNA。这些核糖核酸酶对表达它们的细胞有毒性，为了抵消这种毒性，它们与紧密结合的蛋白抑制剂共同表达。编码这两种蛋白的基因在所有发现它们的原核生物的基因组中相邻。这种抑制剂 - RNA 酶基因的顺序排列符合所谓的毒素 - 抗毒素（TA）模块的排列方式，并且 PIN 结构域 TA 被命名为 VapBC TA（与毒力相关的蛋白，VapB 是包含转录因子结构域的抑制剂，VapC 是 PIN 结构域核糖核酸酶）。大量 vapBC 基因座存在于不同的原核生物中，这促使许多研究人员研究它们的生化和生物学功能。例如，破坏性的人类病原体结核分枝杆菌在其基因组中编码了 45 个 vapBC 基因座，而其非致病性的亲缘种耻垢分枝杆菌只有一个 vapBC 操纵子。在原核生物树的另一个分支上，豆科植物的固氮共生体根瘤菌有 21 个 vapBC 基因座，其中至少一个基因座与植物根瘤中的生长调控有关。这些操纵子被提出了一系列的生物学功能，本综述旨在调查 PIN 结构域，并总结 vapBC TA 系统的当前知识及其在不同细菌中的作用。
