21OU

DRT4 homohexamer

Summary for 21OU

• Entry DOI: 10.2210/pdb21ou/pdb
• EMDB information: 67871
• Descriptor: Reverse transcriptase domain-containing protein, DNA (5'-D(P*AP*AP*AP*AP*AP*AP*AP*A)-3') (2 entities in total)
• Functional Keywords: drt4; reverse transcriptase; terminal transferase; nuclease, rna binding protein/dna, rna binding protein-dna complex
• Biological source: Enterobacteriaceae (enterobacteria); More
• Total number of polymer chains: 12
• Total formula weight: 391869.92

Authors

Xiao, J.,Wang, L. (deposition date: 2025-12-22, release date: 2026-05-27, Last modification date: 2026-06-03)

Primary citation

Rong, X.,Xiao, J.,Zhao, X.,Yan, Y.,Li, J.,Chen, Y.,Fan, Y.,Liu, Z.,Cao, Y.,Chen, F.,Cheng, R.,Wang, X.,Wang, L.,Zhu, B.
DNA polymerization activates RNA cleavage of a reverse transcriptase-like antiviral enzyme.
Science, :eaef3178-eaef3178, 2026

PubMed Abstract: Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3'-guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

PubMed: 42166559
DOI: 10.1126/science.aef3178

Experimental method

ELECTRON MICROSCOPY (2.34 Å)