9LM3

cryo-EM structure of retron Eco2

Summary for 9LM3

• Entry DOI: 10.2210/pdb9lm3/pdb
• EMDB information: 63214
• Descriptor: Retron Ec67 protein, DNA (67-MER), RNA (62-MER), ... (5 entities in total)
• Functional Keywords: rna-mediated retron eco2 oligomerization, rna binding protein/dna/rna, rna binding protein-dna-rna complex
• Biological source: Escherichia coli; More
• Total number of polymer chains: 15
• Total formula weight: 343960.43

Authors

Wang, Y.J.,Wang, C.,Guan, Z.Y.,Zou, T.T. (deposition date: 2025-01-18, release date: 2025-09-17)

Primary citation

Wang, Y.,Wang, C.,Yin, Y.,Cui, Y.,Dai, Z.,Liu, C.,Chen, Y.,Guan, Z.,Zou, T.
Structural basis of the RNA-mediated Retron-Eco2 oligomerization.
Cell Discov, 11:73-73, 2025

PubMed Abstract: In the evolutionary arms race between bacteria and viruses, retrons have emerged as distinctive antiphage defense systems. Here, we elucidate the structure and function of Retron-Eco2, which comprises a non-coding RNA (ncRNA) that encodes multicopy single-stranded DNA (msDNA, a DNA‒RNA hybrid) and a fusion protein containing a reverse transcriptase (RT) domain and a topoisomerase-primase-like (Toprim) effector domain. The Eco2 msDNA and RT-Toprim fusion protein form a 1:1 stoichiometric nucleoprotein complex that further assembles into a trimer (msDNA:RT-Toprim ratio of 3:3) with a distinctive triangular configuration. The RNA portion of the msDNA in one protomer closely intertwines around the RT domain of an adjacent protomer, mediating the formation of this self-inhibitory assembly. Upon activation, the Toprim effector domain exhibits RNase activity, degrading RNA to arrest phage replication. We further reveal that phage mutants evading Eco2-mediated defense harbor mutations in the endonuclease IV-like protein DenB, underscoring DenB's critical role in triggering the activation of this system. Together, these findings provide key structural and functional insights into Retron-Eco2, laying the groundwork for harnessing its potential in biotechnology and synthetic biology applications.

PubMed: 40897710
DOI: 10.1038/s41421-025-00823-y

Experimental method

ELECTRON MICROSCOPY (2.6 Å)