36HT

Retron-Kva2 Complex Composite

36HT の概要

• エントリーDOI: 10.2210/pdb36ht/pdb
• EMDBエントリー: 77585
• 分子名称: Retron-Kva2 Reverse Transcriptase, Retron-Kva2 WH, Retron-Kva2 msdDNA, ... (5 entities in total)
• 機能のキーワード: retron, reverse transcriptase, bacterial immune system, abi, ribonuclease, immune system
• 由来する生物種: Klebsiella variicola; 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 503909.22

構造登録者

Hibshman, G.N. (登録日: 2026-06-10, 公開日: 2026-08-12)

主引用文献

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

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: 42523435
DOI: 10.64898/2026.07.11.737809

実験手法

ELECTRON MICROSCOPY (3.7 Å)