7pq6

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

spinqualitylabelsall models 7pq6, resolution 2.67Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7pq6 is a 2 chain structure with sequence from Sulfolobus islandicus REY15A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.67Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F0NH89_SULIR Publication Abstract from PubMed 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. Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases.,Molina R, Jensen ALG, Marchena-Hurtado J, Lopez-Mendez B, Stella S, Montoya G Nucleic Acids Res. 2021 Dec 2;49(21):12577-12590. doi: 10.1093/nar/gkab1130. PMID:34850143 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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