6nmd

cryo-EM Structure of the LbCas12a-crRNA-AcrVA1 complex

Loading... Status: waiting for Mol* initialization Structural highlights 6nmd is a 3 chain structure with sequence from Atcc baa-1259 and Lachnospiraceae bacterium nd2006. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG Gene: AAX09_07405 (ATCC BAA-1259) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed CRISPR-Cas12a (Cpf1), a type V CRISPR-associated nuclease, provides bacterial immunity against bacteriophages and plasmids but also serves as a tool for genome editing. Foreign nucleic acids are integrated into the CRISPR locus, prompting transcription of CRISPR RNAs (crRNAs) that guide Cas12a cleavage of foreign complementary DNA. However, mobile genetic elements counteract Cas12a with inhibitors, notably type V-A anti-CRISPRs (AcrVAs). We present cryoelectron microscopy structures of Cas12a-crRNA bound to AcrVA1 and AcrVA4 at 3.5 and 3.3 A resolutions, respectively. AcrVA1 is sandwiched between the recognition (REC) and nuclease (NUC) lobes of Cas12a and inserts into the binding pocket for the protospacer-adjacent motif (PAM), a short DNA sequence guiding Cas12a targeting. AcrVA1 cleaves crRNA in a Cas12a-dependent manner, inactivating Cas12a-crRNA complexes. The AcrVA4 dimer is anchored around the crRNA pseudoknot of Cas12a-crRNA, preventing required conformational changes for crRNA-DNA heteroduplex formation. These results uncover molecular mechanisms for CRISPR-Cas12a inhibition, providing insights into bacteria-phage dynamics. Structural Basis for the Inhibition of CRISPR-Cas12a by Anti-CRISPR Proteins.,Zhang H, Li Z, Daczkowski CM, Gabel C, Mesecar AD, Chang L Cell Host Microbe. 2019 May 27. pii: S1931-3128(19)30249-5. doi:, 10.1016/j.chom.2019.05.004. PMID:31155345 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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