Presence of actin binding motif in VgrG-1 toxin of Vibrio cholerae reveals the molecular mechanism of actin cross-linking
Presence of actin binding motif in VgrG-1 toxin of Vibrio cholerae reveals the molecular mechanism of actin cross-linking
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DOI：
10.1016/j.ijbiomac.2019.04.026
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发表时间：
2019-07-15
影响因子：
8.2
通讯作者：
Maiti, Sankar
中科院分区：
文献类型：
--
作者：
Dutta, Priyanka;Jijumon, A. S.;Maiti, Sankar
VI型分泌系统（T6 SS）在霍乱弧菌介导的致病性中起着至关重要的作用。T6 SS的尖端与T4噬菌体的gp 27/gp 5复合物或尾刺同源。霍乱弧菌T6 SS的VgrG-1在其他VgrG中是不寻常的，因为其效应器结构域在其C末端具有额外的肌动蛋白交联结构域（ACD），被转位到真核细胞的胞质溶胶中。VgrG-1的ACD（VgrG-1-ACD）通过肌动蛋白细胞骨架破坏引起T6 SS依赖性宿主细胞的细胞毒性以防止巨噬细胞的细菌吞噬。ACD介导的肌动蛋白交联促进细菌在人类小肠中的存活，沿着其他毒力因子;在人类中建立伴随腹泻发作的成功感染。我们的研究表明，VgrG-1-ACD除了具有肌动蛋白交联活性外，还具有与肌动蛋白结合的能力。ACD的计算分析揭示了肌动蛋白结合基序（ABM）的存在。ABM突变导致体外肌动蛋白结合丧失。具有突变ABM的VgrG-1-ACD不能在体外有效地交联肌动蛋白，并且当转染HeLa细胞时表现出较少的肌动蛋白细胞骨架破坏。(C)2019 Elsevier B. V.版权所有。
Type VI secretion systems (T6SS) plays a crucial role in Vibrio cholerae mediated pathogenicity. Tip of T6SS is homologous to gp27/gp5 complex or tail spike of T4 bacteriophage. VgrG-1 of V. cholerae T6SS is unusual among other VgrG because its effector domain is trans-located into the cytosol of eukaryotic cells with an additional actin cross-linking domain (ACD) at its C terminal end. ACD of VgrG-1 (VgrG-1-ACD) causes T6SS dependent host cell cytotoxicity through actin cytoskeleton disruption to prevent bacterial engulfment by macrophages. ACD mediated actin cross-linking promotes survival of the bacteria in the small intestine of humans, along with other virulence factors; establishes successful infection with the onset of diarrhoea in humans. Our studies demonstrated VgrG-1-ACD can bind to actin besides actin cross-linking activity. Computational analysis of ACD revealed the presence of actin binding motif (ABM). Mutations in ABM lead to loss of actin binding in vitro. VgrG-1-ACD having the mutated ABM cannot cross-link actin efficiently in vitro and manifests less actin cytoskeleton disruption when transfected in HeLa cells. (C) 2019 Elsevier B.V. All rights reserved.