Identification and structural analysis of the tripartite a-pore forming toxin of Aeromonas hydrophila.
Identification and structural analysis of the tripartite a-pore forming toxin of Aeromonas hydrophila.
复制标题
嗜水气单胞菌三方a孔形成毒素的鉴定和结构分析。
DOI：
10.1038/s41467-019-10777-x
复制
发表时间：
2019
影响因子：
16.6
通讯作者：
Wilson JS
中科院分区：
文献类型：
--
作者：
Wilson JS
成孔毒素（α-PFT）的α-螺旋胞溶酶a家族包含单个、两个和三个组成成员。单组分大肠杆菌（eschericia coliClyA）和双组分肠溶耶尔森菌（yersenia enterolyticaYaxAB）的结构都经历了从可溶性到孔形态的构象变化，并发生了寡聚化以产生活性孔。本研究在致病性革兰氏阴性菌（包括嗜水气单胞菌（AhlABC））中发现了三方α-PFTs。我们发现AhlABC毒素需要所有三种成分才能最大限度地裂解细胞。我们提出了描述AhlB中可溶到孔隙过渡的双重铰链机制的孔隙组分结构，以及可溶AhlC采用的对比四聚体组装来隐藏其疏水膜相关残基。我们提出了一种孔隙组装模型，其中AhlC四聚体解离，结合单个膜小叶，招募AhlB促进可溶性向孔隙过渡，在AhlA结合形成活性亲水性衬里孔之前。
The alpha helical CytolysinA family of pore forming toxins (α-PFT) contains single, two, and three component members. Structures of the single componentEschericia coliClyA and the two componentYersinia enterolyticaYaxAB show both undergo conformational changes from soluble to pore forms, and oligomerization to produce the active pore. Here we identify tripartite α-PFTs in pathogenic Gram negative bacteria, includingAeromonas hydrophila(AhlABC). We show that the AhlABC toxin requires all three components for maximal cell lysis. We present structures of pore components which describe a bi-fold hinge mechanism for soluble to pore transition in AhlB and a contrasting tetrameric assembly employed by soluble AhlC to hide their hydrophobic membrane associated residues. We propose a model of pore assembly where the AhlC tetramer dissociates, binds a single membrane leaflet, recruits AhlB promoting soluble to pore transition, prior to AhlA binding to form the active hydrophilic lined pore.