6p8s

From Proteopedia

Structure of P. aeruginosa ATCC27853 HORMA1:HORMA2:Peptide 1 complex

Structural highlights

6p8s is a 6 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CAP7_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] The sensor protein for this CBASS system. Binds to a closure peptide (consensus Glu-Val-Met-Glu-Phe-Asn-Pro), which allows it to activate CdnD for second messenger synthesis.^[3]

Publication Abstract from PubMed

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 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

↑ Ye Q, Lau RK, Mathews IT, Birkholz EA, Watrous JD, Azimi CS, Pogliano J, Jain M, Corbett KD. HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity. Mol Cell. 2019 Dec 31. pii: S1097-2765(19)30922-0. doi:, 10.1016/j.molcel.2019.12.009. PMID:31932165 doi:http://dx.doi.org/10.1016/j.molcel.2019.12.009
↑ Millman A, Melamed S, Amitai G, Sorek R. Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems. Nat Microbiol. 2020 Dec;5(12):1608-1615. doi: 10.1038/s41564-020-0777-y. Epub, 2020 Aug 24. PMID:32839535 doi:http://dx.doi.org/10.1038/s41564-020-0777-y
↑ Ye Q, Lau RK, Mathews IT, Birkholz EA, Watrous JD, Azimi CS, Pogliano J, Jain M, Corbett KD. HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity. Mol Cell. 2019 Dec 31. pii: S1097-2765(19)30922-0. doi:, 10.1016/j.molcel.2019.12.009. PMID:31932165 doi:http://dx.doi.org/10.1016/j.molcel.2019.12.009
↑ Ye Q, Lau RK, Mathews IT, Birkholz EA, Watrous JD, Azimi CS, Pogliano J, Jain M, Corbett KD. HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity. Mol Cell. 2019 Dec 31. pii: S1097-2765(19)30922-0. doi:, 10.1016/j.molcel.2019.12.009. PMID:31932165 doi:http://dx.doi.org/10.1016/j.molcel.2019.12.009