Photorhabdus luminescens TccC3 Toxin Targets the Dynamic Population of F-Actin and Impairs Cell Cortex Integrity.
Photorhabdus luminescens TccC3 Toxin Targets the Dynamic Population of F-Actin and Impairs Cell Cortex Integrity.
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DOI：
10.3390/ijms23137026
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发表时间：
2022-06-24
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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由于其在细胞过程中的重要作用，肌动蛋白是细菌毒素的常见靶标。一种这样的毒素TccC 3是由光杆状菌属的昆虫病原细菌产生的ABC毒素的效应结构域。与其他肌动蛋白靶向毒素不同，TccC 3独特地在Thr-148处ADP-核糖基化肌动蛋白，导致肌动蛋白聚集体的形成和吞噬作用的抑制。已经表明，完全修饰的F-肌动蛋白对cofilin和gelsolin的解聚具有抗性，但它们对部分修饰的肌动蛋白的影响尚未研究。我们发现，只有F-肌动蛋白不受保护的原肌球蛋白是TccC 3的生理底物。然而，ADP-核糖基化的G-肌动蛋白可以产生后cofilin加速F-肌动蛋白解聚，这是只有轻度抑制部分修饰的肌动蛋白。TccC 3-ADP-核糖基化G-肌动蛋白对profilin和胸腺素-β4的亲和力适度减弱，但足以增强它们存在时的自发聚合。有趣的是，Arp 2/3介导的成核也被T148-ADP-核糖基化增强。值得注意的是，即使是部分修饰的肌动蛋白也显示出被质体蛋白和α-辅肌动蛋白捆绑的减少。与这些和其他串联的钙调蛋白同源结构域肌动蛋白组织者在皮质肌动蛋白网络的组装中的作用一致，TccC 3在培养的细胞中诱导强烈的膜起泡。总的来说，我们的数据表明，TccC 3通过影响F-肌动蛋白成核，再循环和与肌动蛋白结合蛋白的相互作用对细胞骨架施加复杂的作用，所述肌动蛋白结合蛋白参与肌动蛋白丝彼此和细胞元件的整合。
Due to its essential role in cellular processes, actin is a common target for bacterial toxins. One such toxin, TccC3, is an effector domain of the ABC-toxin produced by entomopathogenic bacteria of Photorhabdus spp. Unlike other actin-targeting toxins, TccC3 uniquely ADP-ribosylates actin at Thr-148, resulting in the formation of actin aggregates and inhibition of phagocytosis. It has been shown that the fully modified F-actin is resistant to depolymerization by cofilin and gelsolin, but their effects on partially modified actin were not explored. We found that only F-actin unprotected by tropomyosin is the physiological TccC3 substrate. Yet, ADP-ribosylated G-actin can be produced upon cofilin-accelerated F-actin depolymerization, which was only mildly inhibited in partially modified actin. The affinity of TccC3-ADP-ribosylated G-actin for profilin and thymosin-β4 was weakened moderately but sufficiently to potentiate spontaneous polymerization in their presence. Interestingly, the Arp2/3-mediated nucleation was also potentiated by T148-ADP-ribosylation. Notably, even partially modified actin showed reduced bundling by plastins and α-actinin. In agreement with the role of these and other tandem calponin-homology domain actin organizers in the assembly of the cortical actin network, TccC3 induced intense membrane blebbing in cultured cells. Overall, our data suggest that TccC3 imposes a complex action on the cytoskeleton by affecting F-actin nucleation, recycling, and interaction with actin-binding proteins involved in the integration of actin filaments with each other and cellular elements.
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DOI：
10.1126/science.aab4090
发表时间：
2015-07-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Kudryashov DS
影响因子：
4.8
作者：
Heissler, Sarah M.;Chinthalapudi, Krishna;Sellers, James R.
通讯作者：
Sellers, James R.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
7.7
作者：
Funk, Johanna;Merino, Felipe;Bieling, Peter
通讯作者：
Bieling, Peter
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
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通讯作者：
Zwart PH