Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis.
Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis.
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DOI：
10.1038/s41467-022-30373-w
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发表时间：
2022-05-12
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
毒素-抗毒素系统的毒素使用不同的机制来控制细菌生长。在这里，我们专注于结核分枝杆菌的非典型三方毒素-抗毒素-分子伴侣（TAC）系统的有害毒素，其抑制需要抗毒素及其专用SecB样分子伴侣的协同作用。我们表明，TAC毒素是一种真正的核糖核酸酶，并确定确切的切割位点在mRNA靶在体内转录组范围内。在翻译过程中，毒素对mRNA的切割发生在核糖体A位点密码子的第二个核苷酸之后，在体内强烈偏好CCA密码子。最后，我们报告了在天然M存在下核糖体结合的TAC毒素的冷冻电镜结构。tuberculosis cspA mRNA，揭示了TAC毒素与核糖体和P-位点中的tRNA相互作用以切割其mRNA靶标的特异性机制。毒素-抗毒素系统广泛存在于细菌中。本文介绍了M.结核病HigBTAC单独和结合的核糖体在天然cspA mRNA的存在下，阐明其翻译抑制的机制。
Toxins of toxin-antitoxin systems use diverse mechanisms to control bacterial growth. Here, we focus on the deleterious toxin of the atypical tripartite toxin-antitoxin-chaperone (TAC) system of Mycobacterium tuberculosis, whose inhibition requires the concerted action of the antitoxin and its dedicated SecB-like chaperone. We show that the TAC toxin is a bona fide ribonuclease and identify exact cleavage sites in mRNA targets on a transcriptome-wide scale in vivo. mRNA cleavage by the toxin occurs after the second nucleotide of the ribosomal A-site codon during translation, with a strong preference for CCA codons in vivo. Finally, we report the cryo-EM structure of the ribosome-bound TAC toxin in the presence of native M. tuberculosis cspA mRNA, revealing the specific mechanism by which the TAC toxin interacts with the ribosome and the tRNA in the P-site to cleave its mRNA target. Toxin-antitoxin systems are widespread in bacteria. Here the authors present structures of M. tuberculosis HigBTAC alone and bound to the ribosome in the presence of native cspA mRNA, shedding light on its mechanism of translation inhibition.
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影响因子：
13.6
作者：
Agarwal, Sakshi;Sharma, Arun;Singh, Ramandeep
通讯作者：
Singh, Ramandeep
影响因子：
16.6
作者：
Guillet, Valerie;Bordes, Patricia;Mourey, Lionel
通讯作者：
Mourey, Lionel
影响因子：
6.4
作者：
DeJesus MA;Gerrick ER;Xu W;Park SW;Long JE;Boutte CC;Rubin EJ;Schnappinger D;Ehrt S;Fortune SM;Sassetti CM;Ioerger TR
通讯作者：
Ioerger TR
影响因子：
14.9
作者：
Deep A;Tiwari P;Agarwal S;Kaundal S;Kidwai S;Singh R;Thakur KG
通讯作者：
Thakur KG
影响因子：
4
作者：
Fernandez-Garcia, L.;Kim, J. -S.;Wood, T. K.
通讯作者：
Wood, T. K.