9wn1
PhospholipaseA2 with a ligand
Structural highlights
Publication Abstract from PubMedThe cyclic-oligonucleotide-based antiphage signaling system (CBASS) protects bacteria from phage infection. In Vibrio cholerae, phage infection activates CD-NTase DncV to produce 3'3'-cGAMP, which triggers phospholipase CapV to degrade phosphatidylethanolamine and phosphatidylglycerol, the major phospholipids in the inner-membranes, thereby inducing cell death. However, how 3'3'-cGAMP activates CapV was unclear. Here we present crystal structures of inactive Acinetobacter baumannii CapV in apo and 3'3'-cGAMP-bound forms, along with cryo-EM structures of activated CapV-3'3'-cGAMP complex, with or without substrate dioleoylphosphatidyl-ethanolamine (DOPE). Apo-CapV forms symmetric dimers in a "closed" state. 3'3'-cGAMP binding drives lateral polymerization of dimers into filament assembly, inducing an "open" state that exposes the active site and substrate-binding cleft. DOPE binding further shifts CapV to an "ajar" state, where a Y-shaped cleft positions DOPE for hydrolysis via a conserved Ser/Asp catalytic dyad. This 3'3'-cGAMP-induced filamentation mirrors activation mechanisms of TIR-STING, TIR-SAVED, and mammalian STING, revealing a conserved signaling pattern across immune systems. Structural mechanism of 3'3'-cGAMP-induced filamentation and phospholipid hydrolysis by CapV in bacterial antiphage defense.,Lv Y, Liu S, Wang Q, Zhu J, Hou Y, Xu H, Zhu D, Liu Y, Wu J, Wu C, Shang G, Lou H, Lu D, Yuan H, Zhu D Cell Rep. 2026 Apr 13;45(4):117261. doi: 10.1016/j.celrep.2026.117261. PMID:41984589[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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