ACTIN-DIRECTED TOXIN. ACD toxin-produced actin oligomers poison formin-controlled actin polymerization.
ACTIN-DIRECTED TOXIN. ACD toxin-produced actin oligomers poison formin-controlled actin polymerization.
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DOI：
10.1126/science.aab4090
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发表时间：
2015-07-31
期刊：
影响因子：
--
通讯作者：
Kudryashov DS
中科院分区：
文献类型：
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作者：
Heisler DB;Kudryashova E;Grinevich DO;Suarez C;Winkelman JD;Birukov KG;Kotha SR;Parinandi NL;Vavylonis D;Kovar DR;Kudryashov DS
肌动蛋白交联结构域 (ACD) 是一种肌动蛋白特异性毒素，由多种病原体产生，包括危及生命的病原体。霍乱弧菌、创伤弧菌和嗜水气单胞菌。 ACD 引起的肌动蛋白交联被认为会导致缓慢的细胞骨架衰竭，因为肌动蛋白以非功能性寡聚体的形式逐渐隔离。在这里，我们发现 ACD 将细胞质肌动蛋白转化为剧毒寡聚物，有效“毒害”主要肌动蛋白组装蛋白福尔明维持肌动蛋白聚合的能力。因此，ACD 可以通过使用肌动蛋白寡聚物作为次级毒素来靶向最丰富的细胞蛋白，从而有效地破坏肌动蛋白的细胞功能，同时在非常低的剂量下发挥作用。
The actin crosslinking domain (ACD) is an actin-specific toxin produced by several pathogens, including life-threatening spp. of Vibrio cholerae, Vibrio vulnificus, and Aeromonas hydrophila. Actin crosslinking by ACD is thought to lead to slow cytoskeleton failure owing to a gradual sequestration of actin in the form of nonfunctional oligomers. Here we found that ACD converted cytoplasmic actin into highly toxic oligomers that potently “poisoned” the ability of major actin assembly proteins, formins, to sustain actin polymerization. Thus, ACD can target the most abundant cellular protein by employing actin oligomers as secondary toxins to efficiently subvert cellular functions of actin while functioning at very low doses.