The Abi Proteins and Their Involvement in Bacteriocin Self-Immunity
The Abi Proteins and Their Involvement in Bacteriocin Self-Immunity
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DOI：
10.1128/jb.01553-09
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发表时间：
2010-04-15
影响因子：
3.2
通讯作者：
Diep, Dzung B.
中科院分区：
文献类型：
--
作者：
Kjos, Morten;Snipen, Lars;Diep, Dzung B.
Abi蛋白家族由假定的膜结合金属蛋白酶组成。虽然它们参与真核生物中蛋白质的膜锚定，但对它们在原核生物中的功能知之甚少。在一些已知的细菌素基因座中，Abi基因位于细菌素结构基因的下游（如来自植物乳杆菌的pln基因座和来自化脓性链球菌的sag基因座），它们可能与自身免疫有关。通过修改用于从Pfam蛋白家族数据库中选择Abi蛋白的隐马尔可夫模型，我们发现该家族比目前认识的要大。利用细菌素相关Abi基因在测序的基因组中寻找新的细菌素，在革兰氏阳性细菌中发现了7个新的细菌素样基因座。其中一个这样的基因座，取自日本乳酸菌23K，被选中进行进一步的实验研究，证实了细菌素样基因（skkAB）在异源宿主中表达时表现出抗菌活性，并且相关的Abi基因（skkI）赋予对同源细菌素的免疫。对植物乳杆菌Abi基因plnI和Abi样基因plnL的类似研究也证实了它们参与对其同源细菌素（分别为PlnEF和PlnJK）的免疫。有趣的是，来自这三个系统的免疫基因对彼此的细菌素具有高度的交叉免疫，这表明它们识别了一个共同的受体。定点诱变表明，构成Abi蛋白推定的蛋白水解活性位点的保守基序对SkkI的免疫功能至关重要，据我们所知，这代表了自我免疫的新概念。
The Abi protein family consists of putative membrane-bound metalloproteases. While they are involved in membrane anchoring of proteins in eukaryotes, little is known about their function in prokaryotes. In some known bacteriocin loci, Abi genes have been found downstream of bacteriocin structural genes (e. g., pln locus from Lactobacillus plantarum and sag locus from Streptococcus pyogenes), where they probably are involved in self-immunity. By modifying the profile hidden Markov model used to select Abi proteins in the Pfam protein family database, we show that this family is larger than presently recognized. Using bacteriocin-associated Abi genes as a means to search for novel bacteriocins in sequenced genomes, seven new bacteriocin-like loci were identified in Gram-positive bacteria. One such locus, from Lactobacillus sakei 23K, was selected for further experimental study, and it was confirmed that the bacteriocin-like genes (skkAB) exhibited antimicrobial activity when expressed in a heterologous host and that the associated Abi gene (skkI) conferred immunity against the cognate bacteriocin. Similar investigation of the Abi gene plnI and the Abi-like gene plnL from L. plantarum also confirmed their involvement in immunity to their cognate bacteriocins (PlnEF and PlnJK, respectively). Interestingly, the immunity genes from these three systems conferred a high degree of cross-immunity against each other's bacteriocins, suggesting the recognition of a common receptor. Site-directed mutagenesis demonstrated that the conserved motifs constituting the putative proteolytic active site of the Abi proteins are essential for the immunity function of SkkI, and to our knowledge, this represents a new concept in self-immunity.