6p8u
From Proteopedia
Structure of P. aeruginosa ATCC27853 CdnD:HORMA2:Peptide 1 complex
Structural highlights
FunctionCDND_PSEAI 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] Cyclic nucleotide synthase that upon activation catalyzes the synthesis of 3',3',3'-cyclic AMP-AMP-AMP (3',3',3'-c-tri-AMP or cAAA) as the major product, and 3',3'-c-di-AMP as a minor product at pH 8.5. At pH 7.5 also makes 3',3',3'-cyclic AMP-AMP-GMP (cAAG). Binds strongly to ATP and much less well to GTP.[3] 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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