8ZR9

Cryo-EM structure of AbCapV filemant bound with 3',3'-cGAMP

8ZR9 の概要

• エントリーDOI: 10.2210/pdb8zr9/pdb
• EMDBエントリー: 60393
• 分子名称: CGAMP-activated phospholipase CapV, 2-amino-9-[(2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-9-(6-amino-9H-purin-9-yl)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecin-2-yl]-1,9-dihydro-6H-purin-6-one (2 entities in total)
• 機能のキーワード: cbass, hydrolase
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 251890.34

構造登録者

Kong, J.P.,Li, Z.X.,Ke, S.Y.,Xiao, Y.B. (登録日: 2024-06-04, 公開日: 2025-11-19)

主引用文献

Kong, J.,Wu, W.,Ke, S.,Zhou, Z.,Xia, S.,Chen, J.,Zhu, R.,Hou, Y.,Makanyire, T.,Shan, X.,Zhuo, Z.,Li, K.,Shen, H.,Yang, P.,Huang, P.,Liu, J.,Li, J.,Sun, X.,Dong, J.,Sun, H.,Chen, M.,Lu, M.,Li, Z.,Xiao, Y.
Molecular mechanisms of CBASS phospholipase effector CapV mediated membrane disruption.
Nat Commun, 16:8611-8611, 2025

PubMed Abstract: Cyclic oligonucleotide-based antiphage signaling systems (CBASS) are widespread bacterial immune systems that trigger host suicide via cyclic nucleotide-activated effectors. The predominant strategy to induce cell death in CBASS is membrane disruption. Here, we demonstrate that patatin-like phospholipase CapV, the most abundant CBASS effector, relocates and cleaves membrane phospholipids at the cell pole upon 3'3'-cGAMP binding, inducing polarized membrane disruption and cell death. Using cryo-EM, we reveal that apo-CapV adopts both dimeric and tetrameric states, with its phospholipid-binding pocket occluded and locked in an inactive conformation. Binding to 3'3'-cGAMP induces filamentation and substantial conformational change of CapV, enhancing membrane binding via electrostatic interactions between its interspaced basic surfaces and the negatively charged phosphate moieties of phospholipids. Simultaneously, the rearrangement opens the phospholipid-binding pocket, enabling the accommodation of two fatty acid chains of phospholipid within distinct hydrophobic pockets. Our findings reveal a filament-dependent activation mechanism for phospholipase-mediated membrane disruption during antiviral response.

PubMed: 41022836
DOI: 10.1038/s41467-025-63658-x

実験手法

ELECTRON MICROSCOPY (2.7 Å)