Structural mechanism of 3'3'-cGAMP-induced filamentation and phospholipid hydrolysis by CapV in bacterial antiphage defense - PubMed
4 hours ago
- #CBASS defense
- #phospholipase activation
- #structural biology
- The CBASS system protects bacteria from phage infection by activating cell death mechanisms.
- In Vibrio cholerae, phage infection triggers production of 3'3'-cGAMP by CD-NTase DncV, which activates phospholipase CapV.
- CapV degrades phosphatidylethanolamine and phosphatidylglycerol in the inner membrane, leading to cell death.
- Crystal and cryo – EM structures show that apo-CapV forms symmetric dimers in a "closed" state.
- Binding of 3'3'-cGAMP induces lateral polymerization of dimers into filaments, transitioning CapV to an "open" state.
- Substrate binding (e.g., DOPE) shifts CapV to an "ajar" state, positioning phospholipids for hydrolysis via a Ser/Asp catalytic dyad.
- This activation mechanism is similar to that of TIR-STING, TIR-SAVED, and mammalian STING, indicating a conserved immune signaling pattern.