PDF(Pubmed)
Abstract：
Type VII secretion systems are membrane-embedded nanomachines used by Gram-positive bacteria to export effector proteins from the cytoplasm to the extracellular environment. Many of these effectors are polymorphic toxins comprised of an N-terminal Leu-x-Gly (LXG) domain of unknown function and a C-terminal toxin domain that inhibits the growth of bacterial competitors. In recent work, it was shown that LXG effectors require two cognate Lap proteins for T7SS-dependent export. Here, we present the 2.6 Å structure of the LXG domain of the TelA toxin from the opportunistic pathogen Streptococcus intermedius in complex with both of its cognate Lap targeting factors. The structure reveals an elongated α-helical bundle within which each Lap protein makes extensive hydrophobic contacts with either end of the LXG domain. Remarkably, despite low overall sequence identity, we identify striking structural similarity between our LXG complex and PE-PPE heterodimers exported by the distantly related ESX type VII secretion systems of Mycobacteria implying a conserved mechanism of effector export among diverse Gram-positive bacteria. Overall, our findings demonstrate that LXG domains, in conjunction with their cognate Lap targeting factors, represent a tripartite secretion signal for a widespread family of T7SS toxins.
摘要：
VII型分泌系统是革兰氏阳性细菌用于将效应蛋白从细胞质输出到细胞外环境的膜包埋纳米机器。这些效应子中的许多是多态毒素,其包含功能未知的N-末端Leu-x-Gly(LXG)结构域和抑制细菌竞争物生长的C-末端毒素结构域。在最近的工作中,研究表明，LXG效应子需要两种同源Lap蛋白才能依赖T7SS输出。这里,我们展示了来自机会性病原体中间链球菌的TelA毒素LXG域的2.6µ结构，并结合了其两个同源Lap靶向因子。该结构揭示了细长的α-螺旋束，其中每个Lap蛋白与LXG结构域的任一端进行广泛的疏水接触。值得注意的是,尽管整体序列同一性低，我们确定了我们的LXG复合物与分枝杆菌的远缘相关的ESXVII型分泌系统输出的PE-PPE异二聚体之间惊人的结构相似性,这意味着在不同的革兰氏阳性细菌中存在一种保守的效应子输出机制.总的来说,我们的研究结果表明，LXG域，结合他们的同源重叠目标因素，代表广泛的T7SS毒素家族的三方分泌信号。
