9ION

Cryo-EM structure of cUA bound CapE filament

This is a non-PDB format compatible entry.

Summary for 9ION

• Entry DOI: 10.2210/pdb9ion/pdb
• EMDB information: 60745
• Descriptor: cUMP-AMP-activated phospholipase, 3'3'-cUMP-AMP (2 entities in total)
• Functional Keywords: cape, patatin-like phospholipase protein, lipid binding protein
• Biological source: Escherichia coli
• Total number of polymer chains: 4
• Total formula weight: 144169.24

Authors

Gao, A.,Wang, J.G. (deposition date: 2024-07-09, release date: 2025-05-21)

Primary citation

Wang, J.,Li, Z.,Lang, H.,Fu, W.,Gao, Y.,Yin, S.,Sun, P.,Li, Z.,Huang, J.,Liu, S.,Zhu, Y.,Sun, F.,Li, D.,Gao, P.
Cyclic-dinucleotide-induced filamentous assembly of phospholipases governs broad CBASS immunity.
Cell, 2025

PubMed Abstract: Cyclic-oligonucleotide-based antiphage signaling systems (CBASS), a widespread antiviral bacterial immune system homologous to the mammalian cGAS-STING pathway, synthesizes cyclic nucleotide signals and triggers effector proteins to induce cell death and prevent viral propagation. Among various CBASS effectors, phospholipase effectors are the first to be discovered and are one of the most widespread families that sense cyclic dinucleotides to degrade cell membrane phospholipids. Here, we report that CBASS phospholipases assemble from a dimeric inactive state into active higher-order filamentous oligomers upon sensing cyclic dinucleotides. Using a combined approach of cryo-electron microscopy and X-ray crystallography, we have determined the structures of CBASS phospholipase in the inactive dimeric state, the cyclic-dinucleotide-bound active higher-order state, and the substrate-analog-bound catalytic mimicry state, thereby visualizing the complete conformational reorganization process. Complemented by functional assays of intermolecular binding, phospholipase enzymatic activity, in vitro membrane disruption, and in vivo antiphage efficiency, our work elucidates the mechanisms of assembly and activation of CBASS phospholipases.

PubMed: 40345202
DOI: 10.1016/j.cell.2025.04.022

Experimental method

ELECTRON MICROSCOPY (3.27 Å)