7ljl | pdb_00007ljl
Structure of the Enterobacter cloacae CD-NTase CdnD in complex with ATP
Structural highlights
Function[CDND2_ENTCL] 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 II-C(AAG) CBASS system (PubMed:32839535).[1] [2] Cyclic trinucleotide synthase that catalyzes the synthesis of 3',3',3'-cyclic AMP-AMP-GMP as the major product, a second messenger for cell signal transduction.[3] Protects E.coli against phage T2 infection. When the cdnD-cap2-cap3-cap4 operon is introduced in E.coli there is a more than 10(3) decrease in the efficiency of T2 plaque formation. The operon does not protect against phage T5 and only about 10-fold against T7.[4] Publication Abstract from PubMedcGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are signaling proteins that initiate antiviral immunity in animal cells and cyclic-oligonucleotide-based anti-phage signaling system (CBASS) phage defense in bacteria. Upon phage recognition, bacterial CD-NTases catalyze synthesis of cyclic-oligonucleotide signals, which activate downstream effectors and execute cell death. How CD-NTases control nucleotide selection to specifically induce defense remains poorly defined. Here, we combine structural and nucleotide-analog interference-mapping approaches to identify molecular rules controlling CD-NTase specificity. Structures of the cyclic trinucleotide synthase Enterobacter cloacae CdnD reveal coordinating nucleotide interactions and a possible role for inverted nucleobase positioning during product synthesis. We demonstrate that correct nucleotide selection in the CD-NTase donor pocket results in the formation of a thermostable-protein-nucleotide complex, and we extend our analysis to establish specific patterns governing selectivity for each of the major bacterial CD-NTase clades A-H. Our results explain CD-NTase specificity and enable predictions of nucleotide second-messenger signals within diverse antiviral systems. Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense.,Govande AA, Duncan-Lowey B, Eaglesham JB, Whiteley AT, Kranzusch PJ Cell Rep. 2021 Jun 1;35(9):109206. doi: 10.1016/j.celrep.2021.109206. PMID:34077735[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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