9NLV

Cryo-EM structure of hexameric SenDRT9 RT-ncRNA complex

9NLV の概要

• エントリーDOI: 10.2210/pdb9nlv/pdb
• EMDBエントリー: 49523
• 分子名称: RNA-dependent DNA polymerase, RNA (147-MER) (2 entities in total)
• 機能のキーワード: drt9, polymerase, immune system
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 633364.27

構造登録者

Burman, N.,Pandey, S.,Wiedenheft, B.,Sternberg, S.H. (登録日: 2025-03-03, 公開日: 2025-05-14, 最終更新日: 2025-08-13)

主引用文献

Tang, S.,Zedaveinyte, R.,Burman, N.,Pandey, S.,Ramirez, J.L.,Kulber, L.M.,Wiegand, T.,Wilkinson, R.A.,Ma, Y.,Zhang, D.J.,Lampe, G.D.,Berisa, M.,Jovanovic, M.,Wiedenheft, B.,Sternberg, S.H.
Protein-primed homopolymer synthesis by an antiviral reverse transcriptase.
Nature, 643:1352-1362, 2025

PubMed Abstract: Bacteria defend themselves from viral predation using diverse immune systems, many of which target foreign DNA for degradation. Defence-associated reverse transcriptase (DRT) systems provide an intriguing counterpoint to this strategy by using DNA synthesis instead. We and others recently showed that DRT2 systems use an RNA template to assemble a de novo gene that encodes the antiviral effector protein Neo. It remains unclear whether similar mechanisms of defence are used by other related DRT families. Here, we show that DRT9 systems defend against phage using DNA homopolymer synthesis. Viral infection triggers polydeoxyadenylate (poly-dA) accumulation in the cell, driving abortive infection and population-level immunity. Cryo-electron microscopy structures reveal how a non-coding RNA serves as both a structural scaffold and reverse transcription template to direct hexameric complex assembly and poly-dA synthesis. Notably, biochemical and functional experiments identify tyrosine residues within the reverse transcriptase itself that probably prime DNA synthesis, leading to the formation of protein-DNA covalent adducts. Synthesis of poly-dA by DRT9 in vivo is regulated by the competing activities of phage-encoded triggers and host-encoded silencers. Collectively, our study identifies a nucleic-acid-driven defence system that expands the paradigm of bacterial immunity and broadens the known functions of reverse transcriptases.

PubMed: 40436039
DOI: 10.1038/s41586-025-09179-5

実験手法

ELECTRON MICROSCOPY (2.6 Å)