7LJM

Structure of the Salmonella enterica CD-NTase CdnD in complex with GTP

Summary for 7LJM

• Entry DOI: 10.2210/pdb7ljm/pdb
• Descriptor: CD-NTase, MAGNESIUM ION, GUANOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: cd-ntase, cbass, transferase, trinucleotide
• Biological source: Salmonella enterica
• Total number of polymer chains: 2
• Total formula weight: 88922.00

Authors

Govande, A.,Lowey, B.,Eaglesham, J.B.,Whiteley, A.W.,Kranzusch, P.J. (deposition date: 2021-01-29, release date: 2021-06-02, Last modification date: 2024-06-05)

Primary citation

Govande, A.A.,Duncan-Lowey, B.,Eaglesham, J.B.,Whiteley, A.T.,Kranzusch, P.J.
Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense.
Cell Rep, 35:109206-109206, 2021

PubMed Abstract: cGAS/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.

PubMed: 34077735
DOI: 10.1016/j.celrep.2021.109206

Experimental method

X-RAY DIFFRACTION (2.6 Å)