36HT
Retron-Kva2 Complex Composite
Summary for 36HT
| Entry DOI | 10.2210/pdb36ht/pdb |
| EMDB information | 77585 |
| Descriptor | Retron-Kva2 Reverse Transcriptase, Retron-Kva2 WH, Retron-Kva2 msdDNA, ... (5 entities in total) |
| Functional Keywords | retron, reverse transcriptase, bacterial immune system, abi, ribonuclease, immune system |
| Biological source | Klebsiella variicola More |
| Total number of polymer chains | 15 |
| Total formula weight | 503909.22 |
| Authors | |
| Primary citation | Hibshman, G.N.,Wang, L.,MacRae, N.,Zhang, K.,Florez, A.,Shipman, S.L.,Nogales, E. Higher-order assembly of a type IX retron enables exploitation for designer antimicrobials. Biorxiv, 2026 Cited by PubMed Abstract: Bacterial defense systems provide a rich reservoir for biotechnological innovation. Retrons are tripartite abortive infection systems that detect phage invasion using reverse-transcribed DNA (msDNA), but how they structurally couple threat detection to effector activation remains poorly understood. Here, we determine the cryo-EM structure and activation mechanism of retron-Kva2, a type IX retron from the human pathogen . We reveal that retron-Kva2 assembles into an asymmetric, higher-order ribonucleoprotein complex that sequesters a toxic dimeric HEPN RNase at its core. We identify a natural phage trigger as the phage T5 protein D5, which activates the retron through structural mimicry. Mirroring the retron-Kva2 winged-helix protein, the helix-turn-helix fold of D5 binds the msDNA sensor, driving conformational remodeling that unleashes HEPN-mediated tRNA cleavage and growth arrest. Because retron-Kva2 surveils a structural fold via msDNA binding, rather than a primary sequence, this recognition mechanism provides a broadly exploitable pathway for programmable activation. Harnessing this structure-based logic, we computationally designed synthetic triggers that activate retron-Kva2-mediated bacterial growth arrest . Our findings reveal the architectural basis of type IX retron immunity and establish a structure-guided paradigm for repurposing bacterial defense systems into precision-honed antimicrobial therapeutics. PubMed: 42523435DOI: 10.64898/2026.07.11.737809 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.7 Å) |
Structure validation
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