6p8v
From Proteopedia
Structure of E. coli MS115-1 HORMA:CdnC:Trip13 complex
Structural highlights
FunctionCAP6_ECOM1 CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophage. The CD-NTase protein synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection. A type III-C(AAA) CBASS system (PubMed:32839535).[1] [2] Binds and disassembles an active CdnC:Cap7 (Cap7 is also called HORMA) complex, inhibiting the complex's ability to synthesize cyclic nucleotide second messengers (PubMed:31932165). An AAA+-ATPase remodeler, it is thought that in the absence of foreign threat Cap6 (also called Trip13) maintains the Cap7 protein in its open, inactive state. Once activated (presumably by a bacteriophage protein) Cap7 binds to and activates its cognate CD-NTase (CdnC in this bacteria) to synthesize cAAA, a cyclic nucleotide second messenger. cAAA activates the NucC endonuclease which degrades all DNA in the infected cell, causing cell death and abortive phage infection (Probable).[3] [4] Protects E.coli strain JP313 against bacteriophage lambda cI- infection. When the cdnC-cap7-cap6-nucC operon is transformed into a susceptible E.coli strain it confers bacteriophage lambda cI- immunity. Mutations in the sensor (Cap7 also called HORMA) or effector proteins (CdnC, NucC) but not the disassembly protein (Cap6 also called Trip13) no longer confer immunity. The presence of the intact operon leads to culture collapse and cell death, which occurs before the phage has finished its replication cycle, thus protecting non-infected bacteria by aborting the phage infection and preventing its propagation.[5] Publication Abstract from PubMedBacteria 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 lambda 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. HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity.,Ye Q, Lau RK, Mathews IT, Birkholz EA, Watrous JD, Azimi CS, Pogliano J, Jain M, Corbett KD Mol Cell. 2019 Dec 31. pii: S1097-2765(19)30922-0. doi:, 10.1016/j.molcel.2019.12.009. PMID:31932165[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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