7PQ6

Crystal Structure of the Ring Nuclease 0811 mutant-S12A from Sulfolobus islandicus (Sis0811)

This is a non-PDB format compatible entry.

Summary for 7PQ6

• Entry DOI: 10.2210/pdb7pq6/pdb
• Related: 7PQ2 7PQ3
• Descriptor: CRISPR-associated protein, APE2256 family (2 entities in total)
• Functional Keywords: ring nuclease, crispr-associated protein, helix-turn-helix, antiviral protein, viral resistance, carf nucleotide-binding domain, crispr ring nuclease
• Biological source: Sulfolobus islandicus REY15A
• Total number of polymer chains: 2
• Total formula weight: 63276.27

Authors

Molina, R.,Jensen, A.L.G.,Marchena-Hurtado, J.,Lopez-Mendez, B.,Stella, S.,Montoya, G. (deposition date: 2021-09-16, release date: 2021-11-24, Last modification date: 2024-01-31)

Primary citation

Molina, R.,Jensen, A.L.G.,Marchena-Hurtado, J.,Lopez-Mendez, B.,Stella, S.,Montoya, G.
Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases.
Nucleic Acids Res., 49:12577-12590, 2021

PubMed Abstract: Type III CRISPR-Cas effector systems detect foreign RNA triggering DNA and RNA cleavage and synthesizing cyclic oligoadenylate molecules (cA) in their Cas10 subunit. cAs act as a second messenger activating auxiliary nucleases, leading to an indiscriminate RNA degradation that can end in cell dormancy or death. Standalone ring nucleases are CRISPR ancillary proteins which downregulate the strong immune response of Type III systems by degrading cA. These enzymes contain a CRISPR-associated Rossman-fold (CARF) domain, which binds and cleaves the cA molecule. Here, we present the structures of the standalone ring nuclease from Sulfolobus islandicus (Sis) 0811 in its apo and post-catalytic states. This enzyme is composed by a N-terminal CARF and a C-terminal wHTH domain. Sis0811 presents a phosphodiester hydrolysis metal-independent mechanism, which cleaves cA4 rings to generate linear adenylate species, thus reducing the levels of the second messenger and switching off the cell antiviral state. The structural and biochemical analysis revealed the coupling of a cork-screw conformational change with the positioning of key catalytic residues to proceed with cA4 phosphodiester hydrolysis in a non-concerted manner.

PubMed: 34850143
DOI: 10.1093/nar/gkab1130

Experimental method

X-RAY DIFFRACTION (2.67 Å)