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HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity.
Molecular Cell ( IF 14.5 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.molcel.2019.12.009 Qiaozhen Ye 1 , Rebecca K Lau 2 , Ian T Mathews 3 , Erica A Birkholz 4 , Jeramie D Watrous 5 , Camillia S Azimi 1 , Joe Pogliano 4 , Mohit Jain 6 , Kevin D Corbett 7
Molecular Cell ( IF 14.5 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.molcel.2019.12.009 Qiaozhen Ye 1 , Rebecca K Lau 2 , Ian T Mathews 3 , Erica A Birkholz 4 , Jeramie D Watrous 5 , Camillia S Azimi 1 , Joe Pogliano 4 , Mohit Jain 6 , Kevin D Corbett 7
Affiliation
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Bacteria are continually challenged by foreign invaders, including bacteriophages, and have evolved a variety of defenses against these invaders. Here, we describe the structural and biochemical mechanisms of a bacteriophage immunity pathway found in a broad array of bacteria, including E. coli and Pseudomonas aeruginosa. This pathway uses eukaryotic-like HORMA domain proteins that recognize specific peptides, then bind and activate a cGAS/DncV-like nucleotidyltransferase (CD-NTase) to generate a cyclic triadenylate (cAAA) second messenger; cAAA in turn activates an endonuclease effector, NucC. Signaling is attenuated by a homolog of the AAA+ ATPase Pch2/TRIP13, which binds and disassembles the active HORMA-CD-NTase complex. When expressed in non-pathogenic E. coli, this pathway confers immunity against bacteriophage λ through an abortive infection mechanism. Our findings reveal the molecular mechanisms of a bacterial defense pathway integrating a cGAS-like nucleotidyltransferase with HORMA domain proteins for threat sensing through protein detection and negative regulation by a Trip13 ATPase.
中文翻译：
HORMA域蛋白和Trip13样ATPase调节细菌cGAS样酶来介导噬菌体免疫。
细菌不断受到包括噬菌体在内的外来入侵者的挑战，并已发展出多种针对这些入侵者的防御措施。在这里，我们描述了在包括大肠杆菌和铜绿假单胞菌在内的多种细菌中发现的噬菌体免疫途径的结构和生化机制。该途径利用真核样HORMA结构域蛋白识别特定的肽，然后结合并激活cGAS / DncV样核苷酸转移酶（CD-NTase）生成环状三腺苷酸（cAAA）第二信使。cAAA继而激活核酸内切酶效应子NucC。信号被AAA + ATPase Pch2 / TRIP13的同源物减弱，该同源物结合并分解了活性HORMA-CD-NTase复合物。在非致病性大肠杆菌中表达时，该途径通过流产感染机制赋予针对噬菌体λ的免疫力。我们的发现揭示了一种细菌防御途径的分子机制，该途径将cGAS样核苷酸转移酶与HORMA域蛋白整合在一起，可通过蛋白质检测和Trip13 ATPase的负调控来进行威胁感测。
更新日期：2020-01-11
中文翻译：
HORMA域蛋白和Trip13样ATPase调节细菌cGAS样酶来介导噬菌体免疫。
细菌不断受到包括噬菌体在内的外来入侵者的挑战，并已发展出多种针对这些入侵者的防御措施。在这里，我们描述了在包括大肠杆菌和铜绿假单胞菌在内的多种细菌中发现的噬菌体免疫途径的结构和生化机制。该途径利用真核样HORMA结构域蛋白识别特定的肽，然后结合并激活cGAS / DncV样核苷酸转移酶（CD-NTase）生成环状三腺苷酸（cAAA）第二信使。cAAA继而激活核酸内切酶效应子NucC。信号被AAA + ATPase Pch2 / TRIP13的同源物减弱，该同源物结合并分解了活性HORMA-CD-NTase复合物。在非致病性大肠杆菌中表达时，该途径通过流产感染机制赋予针对噬菌体λ的免疫力。我们的发现揭示了一种细菌防御途径的分子机制，该途径将cGAS样核苷酸转移酶与HORMA域蛋白整合在一起，可通过蛋白质检测和Trip13 ATPase的负调控来进行威胁感测。
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