8FMG

Structure of CBASS Cap5 from Pseudomonas syringae as an activated tetramer with the cyclic dinucleotide 3'2'-c-diAMP ligand (3 tetramers in the AU)

8FMG の概要

• エントリーDOI: 10.2210/pdb8fmg/pdb
• 分子名称: SAVED domain-containing protein, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: cyclic dinucleotide, bacterial immunity, cbass, cap5 effector dna endonuclease, viral defense, immune system
• 由来する生物種: Pseudomonas syringae
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 522232.67

構造登録者

Rechkoblit, O.,Kreitler, D.F.,Aggarwal, A.K. (登録日: 2022-12-23, 公開日: 2024-02-07, 最終更新日: 2024-05-29)

主引用文献

Rechkoblit, O.,Sciaky, D.,Kreitler, D.F.,Buku, A.,Kottur, J.,Aggarwal, A.K.
Activation of CBASS Cap5 endonuclease immune effector by cyclic nucleotides.
Nat.Struct.Mol.Biol., 31:767-776, 2024

PubMed Abstract: The bacterial cyclic oligonucleotide-based antiphage signaling system (CBASS) is similar to the cGAS-STING system in humans, containing an enzyme that synthesizes a cyclic nucleotide on viral infection and an effector that senses the second messenger for the antiviral response. Cap5, containing a SAVED domain coupled to an HNH DNA endonuclease domain, is the most abundant CBASS effector, yet the mechanism by which it becomes activated for cell killing remains unknown. We present here high-resolution structures of full-length Cap5 from Pseudomonas syringae (Ps) with second messengers. The key to PsCap5 activation is a dimer-to-tetramer transition, whereby the binding of second messenger to dimer triggers an open-to-closed transformation of the SAVED domains, furnishing a surface for assembly of the tetramer. This movement propagates to the HNH domains, juxtaposing and converting two HNH domains into states for DNA destruction. These results show how Cap5 effects bacterial cell suicide and we provide proof-in-principle data that the CBASS can be extrinsically activated to limit bacterial infections.

PubMed: 38321146
DOI: 10.1038/s41594-024-01220-x

実験手法

X-RAY DIFFRACTION (1.79 Å)