6rj9

Cryo-EM structure of St1Cas9-sgRNA-tDNA20-AcrIIA6 monomeric assembly.Cryo-EM structure of St1Cas9-sgRNA-tDNA20-AcrIIA6 monomeric assembly.

6rj9, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Structural highlights 6rj9 is a 5 chain structure with sequence from [1], Atcc 19258 and Streptococcus phage d1811. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 6rja, 6rjd, 6rjg Gene: D1811_026 (Streptococcus phage D1811), cas9, CDA68_00396 (ATCC 19258) Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed In the arms race against bacteria, bacteriophages have evolved diverse anti-CRISPR proteins (Acrs) that block CRISPR-Cas immunity. Acrs play key roles in the molecular coevolution of bacteria with their predators, use a variety of mechanisms of action, and provide tools to regulate Cas-based genome manipulation. Here, we present structural and functional analyses of AcrIIA6, an Acr from virulent phages, exploring its unique anti-CRISPR action. Our cryo-EM structures and functional data of AcrIIA6 binding to Streptococcus thermophilus Cas9 (St1Cas9) show that AcrIIA6 acts as an allosteric inhibitor and induces St1Cas9 dimerization. AcrIIA6 reduces St1Cas9 binding affinity for DNA and prevents DNA binding within cells. The PAM and AcrIIA6 recognition sites are structurally close and allosterically linked. Mechanistically, AcrIIA6 affects the St1Cas9 conformational dynamics associated with PAM binding. Finally, we identify a natural St1Cas9 variant resistant to AcrIIA6 illustrating Acr-driven mutational escape and molecular diversification of Cas9 proteins. Cas9 Allosteric Inhibition by the Anti-CRISPR Protein AcrIIA6.,Fuchsbauer O, Swuec P, Zimberger C, Amigues B, Levesque S, Agudelo D, Duringer A, Chaves-Sanjuan A, Spinelli S, Rousseau GM, Velimirovic M, Bolognesi M, Roussel A, Cambillau C, Moineau S, Doyon Y, Goulet A Mol Cell. 2019 Sep 26. pii: S1097-2765(19)30697-5. doi:, 10.1016/j.molcel.2019.09.012. PMID:31604602 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.