9NNH

Cryo-EM structure of the Retron Ec78 complex, PtuA:PtuB:RT (4:2:2)

Summary for 9NNH

• Entry DOI: 10.2210/pdb9nnh/pdb
• EMDB information: 49575
• Descriptor: Retron I-A effector PtuA, Retron I-A effector PtuB, Retron I-A Ec78 reverse transcriptase, ... (6 entities in total)
• Functional Keywords: retron; ncrna; msdna, dna-rna hybrid
• Biological source: Escherichia coli; More
• Total number of polymer chains: 12
• Total formula weight: 467079.49

Authors

Wang, B.,Li, H. (deposition date: 2025-03-05, release date: 2025-10-08, Last modification date: 2025-11-12)

Primary citation

Wang, B.,Hoffman, R.D.,Hou, Y.M.,Li, H.
Structural basis for retron co-option of anti-phage ATPase-nuclease.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Retrons have been recently identified as bacterial defense systems that employ a tripartite of reverse transcriptase, non-coding RNA (ncRNA) and its derived multi-copy single stranded DNA (msDNA) to sequester effector activity. Phage invasion activates retrons, triggering effector activity and inducing abortive infection and cell growth arrest. Ec78 differs from other retrons by leveraging the Septu defense system, a stand-alone ATPase-nuclease pair (PtuAB), by reshaping the phage sensing and molecular assembly processes of PtuAB. To elucidate how Ec78 hijacks PtuAB, we determined electron cryomicroscopy structures of Ec78 as well as the retron-displaced PtuAB. We show that the Ec78-associated ATPase, PtuA, acquired unique elements that enable its interactions with the reverse transcriptase and the msDNA, and self-assembly when displaced by the retron. By biochemical and mutational analyses, we also show that the retron-displaced PtuAB forms a tetramer, unlike its stand-alone counterpart, that restricts the host. However, in the presence of the retron, the retron-displaced PtuAB confers a well-controlled immune response, eliciting ATP hydrolysis- and msDNA-regulated targeting to host factors. Our studies reveal an evolutionary principle for retrons to co-opt conserved enzyme modules for defense in response to different cellular needs.

PubMed: 41174277
DOI: 10.1038/s41594-025-01702-6

Experimental method

ELECTRON MICROSCOPY (2.69 Å)