8D4B
Structure of Cas12a2 ternary complex
Summary for 8D4B
| Entry DOI | 10.2210/pdb8d4b/pdb |
| EMDB information | 27180 |
| Descriptor | OrfB_Zn_ribbon domain-containing protein, RNA (41-MER), RNA (28-MER) (3 entities in total) |
| Functional Keywords | cas12a2, crispr, nuclease, dna binding protein-rna complex, dna binding protein/rna |
| Biological source | Sulfuricurvum sp. PC08-66 More |
| Total number of polymer chains | 3 |
| Total formula weight | 165258.91 |
| Authors | Bravo, J.P.K.,Taylor, D.W. (deposition date: 2022-06-01, release date: 2023-01-18, Last modification date: 2024-06-12) |
| Primary citation | Bravo, J.P.K.,Hallmark, T.,Naegle, B.,Beisel, C.L.,Jackson, R.N.,Taylor, D.W. RNA targeting unleashes indiscriminate nuclease activity of CRISPR-Cas12a2. Nature, 613:582-587, 2023 Cited by PubMed Abstract: 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. 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. PubMed: 36599980DOI: 10.1038/s41586-022-05560-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.92 Å) |
Structure validation
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