9DIF

CBASS Pseudomonas syringae Cap5 tetramer with DNA duplex and 3'2'-c-GAMP cyclic dinucleotide ligand

Summary for 9DIF

• Entry DOI: 10.2210/pdb9dif/pdb
• Related: 8FM1 8FMF 8FMG 8FMH
• Descriptor: HNH endonuclease, DNA (5'-D(*TP*TP*GP*CP*TP*CP*TP*CP*TP*TP*AP*AP*GP*AP*GP*AP*GP*CP*A)-3'), 3'2'-cGAMP, ... (5 entities in total)
• Functional Keywords: bacterial immunity, cbass, cyclic dinucleotide, cap5 effector dna endonuclease, viral defense, hnh endonuclease, dna, immune system
• Biological source: Pseudomonas syringae; More
• Total number of polymer chains: 3
• Total formula weight: 92703.76

Authors

Rechkoblit, O.,Aggarwal, A.K. (deposition date: 2024-09-05, release date: 2025-06-18)

Primary citation

Rechkoblit, O.,Sciaky, D.,Ni, M.,Li, Y.,Kottur, J.,Fang, G.,Aggarwal, A.K.
Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector.
Nat Commun, 16:5243-5243, 2025

PubMed Abstract: Bacterial CBASS immune defense systems commonly kill virally infected cells by degrading genomic DNA in a form of cell suicide or abortive infection. We present a high-resolution structure of the CBASS effector Cap5, activated by a cyclic nucleotide, in the act of digesting DNA via tetrameric HNH endonuclease domains. Two HNH domains are in a catalytically active state for cleavage of the DNA strands, whereas the other two HNH domains are in a topologically distinct catalytically inactive state for simply DNA binding. The four HNH domains track one face of the DNA and mark an enzyme that acts as a stand-alone non-specific nuclease. We also show that chromosomally encoded CBASS Cap5 can be extrinsically activated by a cyclic nucleotide, as a step towards potential antibiotics.

PubMed: 40473611
DOI: 10.1038/s41467-025-60484-z

Experimental method

X-RAY DIFFRACTION (1.67 Å)