7Z56

Crystal Structure of the Ring Nuclease 0455 from Sulfolobus islandicus (Sis0455) in its apo form

This is a non-PDB format compatible entry.

Summary for 7Z56

• Entry DOI: 10.2210/pdb7z56/pdb
• Related: 7Z55
• Descriptor: CRISPR-associated protein (2 entities in total)
• Functional Keywords: ring nuclease, crispr-associated protein, 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: 47258.38

Authors

Molina, R.,Martin-Garcia, R.,Lopez-Mendez, B.,Jensen, A.L.G.,Marchena-Hurtado, J.,Stella, S.,Montoya, G. (deposition date: 2022-03-08, release date: 2022-11-23, Last modification date: 2024-10-16)

Primary citation

Molina, R.,Garcia-Martin, R.,Lopez-Mendez, B.,Jensen, A.L.G.,Ciges-Tomas, J.R.,Marchena-Hurtado, J.,Stella, S.,Montoya, G.
Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases.
Nucleic Acids Res., 50:11199-11213, 2022

PubMed Abstract: Standalone ring nucleases are CRISPR ancillary proteins, which downregulate the immune response of Type III CRISPR-Cas systems by cleaving cyclic oligoadenylates (cA) second messengers. Two genes with this function have been found within the Sulfolobus islandicus (Sis) genome. They code for a long polypeptide composed by a CARF domain fused to an HTH domain and a short polypeptide constituted by a CARF domain with a 40 residue C-terminal insertion. Here, we determine the structure of the apo and substrate bound states of the Sis0455 enzyme, revealing an insertion at the C-terminal region of the CARF domain, which plays a key role closing the catalytic site upon substrate binding. Our analysis reveals the key residues of Sis0455 during cleavage and the coupling of the active site closing with their positioning to proceed with cA4 phosphodiester hydrolysis. A time course comparison of cA4 cleavage between the short, Sis0455, and long ring nucleases, Sis0811, shows the slower cleavage kinetics of the former, suggesting that the combination of these two types of enzymes with the same function in a genome could be an evolutionary strategy to regulate the levels of the second messenger in different infection scenarios.

PubMed: 36271789
DOI: 10.1093/nar/gkac923

Experimental method

X-RAY DIFFRACTION (2.27 Å)