9HM6
Structure of Ba1Cas12a3 ternary complex
Summary for 9HM6
| Entry DOI | 10.2210/pdb9hm6/pdb |
| EMDB information | 52287 |
| Descriptor | Ba1Cas12a3, crRNA, target RNA (3 entities in total) |
| Functional Keywords | crispar cas nuclease, rna binding protein |
| Biological source | Bacteroidetes bacterium HGW-Bacteroidetes-12 More |
| Total number of polymer chains | 3 |
| Total formula weight | 169455.98 |
| Authors | Yuan, B.,Heinz, D.W. (deposition date: 2024-12-06, release date: 2025-12-17, Last modification date: 2026-05-27) |
| Primary citation | Dmytrenko, O.,Yuan, B.,Crosby, K.T.,Krebel, M.,Chen, X.,Nowak, J.S.,Chramiec-Glabik, A.,Filani, B.,Gribling-Burrer, A.S.,van der Toorn, W.,von Kleist, M.,Achmedov, T.,Smyth, R.P.,Glatt, S.,Bravo, J.P.K.,Heinz, D.W.,Jackson, R.N.,Beisel, C.L. RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity. Nature, 649:1312-1321, 2026 Cited by PubMed Abstract: In all domains of life, tRNAs mediate the transfer of genetic information from mRNAs to proteins. As their depletion suppresses translation and, consequently, viral replication, tRNAs represent long-standing and increasingly recognized targets of innate immunity. Here we report Cas12a3 effector nucleases from type V CRISPR-Cas adaptive immune systems in bacteria that preferentially cleave tRNAs after recognition of target RNA. Cas12a3 orthologues belong to one of two previously unreported nuclease clades that exhibit RNA-mediated cleavage of non-target RNA, and are distinct from all other known type V systems. Through cell-based and biochemical assays and direct RNA sequencing, we demonstrate that recognition of a complementary target RNA by the CRISPR RNA triggers Cas12a3 to cleave the conserved 5'-CCA-3' tail of diverse tRNAs to drive growth arrest and anti-phage defence. Cryogenic electron microscopy structures further revealed a distinct tRNA-loading domain that positions the tRNA tail in the RuvC active site of the nuclease. By designing synthetic reporters that mimic the tRNA acceptor stem and tail, we expanded the capacity of current CRISPR-based diagnostics for multiplexed RNA detection. Overall, these findings reveal widespread tRNA inactivation as a previously unrecognized CRISPR-based immune strategy that broadens the application space of the existing CRISPR toolbox. PubMed: 41501459DOI: 10.1038/s41586-025-09852-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4 Å) |
Structure validation
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