Bifunctional Immunity Proteins Protect Bacteria against FtsZ-Targeting ADP-Ribosylating Toxins.
Bifunctional Immunity Proteins Protect Bacteria against FtsZ-Targeting ADP-Ribosylating Toxins.
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DOI：
10.1016/j.cell.2018.09.037
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发表时间：
2018-11-15
期刊：
影响因子：
64.5
通讯作者：
Mougous JD
中科院分区：
文献类型：
--
作者：
Ting SY;Bosch DE;Mangiameli SM;Radey MC;Huang S;Park YJ;Kelly KA;Filip SK;Goo YA;Eng JK;Allaire M;Veesler D;Wiggins PA;Peterson SB;Mougous JD
蛋白质的ADP-核糖基化可以深刻地影响它们的功能，并且作为细菌毒素损害真核细胞过程的有效机制。在这里，我们报告的发现，细菌也采用ADP-核糖基化毒素对彼此在种间竞争。我们证明，一个这样的毒素从变形斑沙雷氏菌中断竞争细胞的分裂，通过修改基本的细菌微管蛋白样蛋白，FtsZ，邻近其原聚体接口，阻止其能力，以抑制。毒素与其免疫决定簇复合的结构揭示了两种不同的抑制模式：活性位点封闭和ADP-核糖修饰的酶促去除。我们表明，每一个都足以支持毒素免疫，然而，后者还提供了前所未有的广泛的保护，对非同源ADP-核糖基化效应。我们的研究结果揭示了细菌间的军备竞赛如何产生一种独特的解决方案，以保护细菌细胞分裂机制的完整性，防止失活翻译后修饰。细菌间竞争的一种广泛保守的毒素靶向ADP-核糖基化的蛋白质，而抗毒素则使用活性位点封闭和酶促逆转修饰的双重机制进行反击，从而赋予对不同毒素的广泛免疫力。
ADP-ribosylation of proteins can profoundly impact their function and serves as an effective mechanism by which bacterial toxins impair eukaryotic cell processes. Here we report the discovery that bacteria also employ ADP-ribosylating toxins against each other during interspecies competition. We demonstrate that one such toxin from Serratia proteamaculans interrupts the division of competing cells by modifying the essential bacterial tubulin-like protein, FtsZ, adjacent to its protomer interface, blocking its capacity to polymerize. The structure of the toxin in complex with its immunity determinant revealed two distinct modes of inhibition: active site occlusion and enzymatic removal of ADP-ribose modifications. We show that each is sufficient to support toxin immunity; however, the latter additionally provides unprecedented broad protection against non-cognate ADP-ribosylating effectors. Our findings reveal how an interbacterial arms race has produced a unique solution for safeguarding the integrity of bacterial cell division machinery against inactivating post-translational modifications. A widely conserved toxin for interbacterial competition targets proteins for ADP-ribosylation, while antitoxins fight back using dual mechanisms of active site occlusion and enzymatic reversal of the modification, conferring broad immunity to diverse toxins.
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影响因子：
--
作者：
Aravind L;Zhang D;de Souza RF;Anand S;Iyer LM
通讯作者：
Iyer LM
影响因子：
4.5
作者：
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作者：
Jankevicius, Gytis;Ariza, Antonio;Ahel, Marijan;Ahel, Ivan
通讯作者：
Ahel, Ivan
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
DOI：
10.1101/sqb.1969.034.01.069
发表时间：
1969-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
HONJO, T;NISHIZUKA, Y;HAYAISHI, O
通讯作者：
HAYAISHI, O