9YLV
Cryo-EM structure of apo CbCash dodecamer
Summary for 9YLV
| Entry DOI | 10.2210/pdb9ylv/pdb |
| EMDB information | 73094 |
| Descriptor | CbCash (1 entity in total) |
| Functional Keywords | trna endonuclease, ca4 activation, crispr associated schlafen, csx15, rna binding protein |
| Biological source | Chloroflexia |
| Total number of polymer chains | 12 |
| Total formula weight | 402367.60 |
| Authors | Liu, Y.,Weickert, P.,Strecker, J. (deposition date: 2025-10-09, release date: 2026-04-29, Last modification date: 2026-07-15) |
| Primary citation | Weickert, P.,Liu, Y.,Strecker, J. Prokaryotic Schlafen proteins cleave tRNAs during type III CRISPR immunity. Nat Commun, 2026 Cited by PubMed Abstract: Schlafen nucleases restrict viral infection in mammals by cleaving self RNAs, however, their function and mechanism in prokaryotic immunity is unknown. Here, we uncover CRISPR-associated Schlafen (Cash) proteins containing a Schlafen domain fused to Csx15, an uncharacterized member of Rossmann-like nucleotide-binding sensors. Cash is activated by cyclic tetra-adenylate (cA₄) produced during type III CRISPR interference and induces cell toxicity by cleaving tRNAs, primarily in the T-loop. Cryo-electron microscopy structures of Chloroflexi bacterium Cash reveal an inactive dodecamer, the formation of a filament upon cA₄ binding to align catalytic interfaces, and the molecular basis of substrate recognition and cleavage in a tRNA-bound complex. We identify numerous families of prokaryotic Schlafen proteins associated with diverse antiviral defense systems and characterized by unique sensor domains. This work highlights tRNA depletion by Schlafen nucleases as an evolutionary recurring antiviral strategy and reveals mechanistic differences between Cash and human Schlafen members. PubMed: 42393087DOI: 10.1038/s41467-026-74880-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.86 Å) |
Structure validation
Download full validation report
