9TET

Oligomerisation of type III CRISPR-associated Csx15 to regulate antiviral signalling

Summary for 9TET

• Entry DOI: 10.2210/pdb9tet/pdb
• Descriptor: CRISPR-associated Csx15, GLYCEROL, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: ring nuclease crispr bacterial defense, viral protein
• Biological source: Pseudomonas fluorescens
• Total number of polymer chains: 1
• Total formula weight: 16053.27

Authors

McMahon, S.A.,Chi, H.,Graham, S.,White, M.F. (deposition date: 2025-11-26, release date: 2026-04-15, Last modification date: 2026-04-29)

Primary citation

Chi, H.,McMahon, S.A.,Graham, S.,White, M.F.
The CRISPR ring nuclease Csx15 oligomerises on cyclic nucleotide binding to regulate antiviral defence.
Biochem.J., 483:699-712, 2026

PubMed Abstract: Prokaryotic type III CRISPR systems signal infection by generating cyclic oligoadenylate (cOA) second messengers, which activate defence proteins allosterically, providing immunity. cOA molecules are typically degraded by extrinsic, stand-alone ring nuclease (RN) enzymes with phosphodiesterase activity, or by the intrinsic RN activity of the effectors themselves. Viruses and plasmids also encode RNs, which can function as anti-CRISPRs (Acr). Eight different families of extrinsic RNs are currently known. Here, we report the structural and biochemical analysis of one of these families: Csx15. We show that Csx15 is a dimeric protein of the CARF (CRISPR associated Rossmann fold) superfamily with the ability to bind cyclic tetra-adenylate (cA4) molecules in a shared binding site formed by the head-to-tail stacking of dimers in a filament conformation. Some family members are non-enzymatic, relying on the sequestration (sponging) of cA4 to regulate the host immune response, while others act as canonical RNs, slowly degrading cA4.

PubMed: 41911342
DOI: 10.1042/BCJ20260019

Experimental method

X-RAY DIFFRACTION (1.88 Å)