8d49

Structure of Cas12a2 binary complex

spinqualitylabelsall models 8d49, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8d49 is a 2 chain structure with sequence from Sulfuricurvum sp. PC08-66 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0C2W1L1_9BACT Publication Abstract from PubMed Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided, sequence-nonspecific degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA following recognition of a complementary RNA target, culminating in abortive infection(1). Here we report structures of Cas12a2 in binary, ternary and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC active site within a large, positively charged cleft. Double-stranded DNA substrates are captured through duplex distortion and local melting, stabilized by pairs of 'aromatic clamp' residues that are crucial for double-stranded DNA degradation and in vivo immune system function. Our work provides a structural basis for this mechanism of abortive infection to achieve population-level immunity, which can be leveraged to create rational mutants that degrade a spectrum of collateral substrates. RNA targeting unleashes indiscriminate nuclease activity of CRISPR-Cas12a2.,Bravo JPK, Hallmark T, Naegle B, Beisel CL, Jackson RN, Taylor DW Nature. 2023 Jan;613(7944):582-587. doi: 10.1038/s41586-022-05560-w. Epub 2023 , Jan 4. PMID:36599980 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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