Anti-phage defense mechanism involving phage-encoded DNA binding protein and bacterial reverse transcriptase DRT4.

ABSTRACT: Prokaryotic defense-associated reverse transcriptase (DRT) systems confer host resistance to viral infection through DNA synthesis; however, the molecular mechanisms underlying their function remain poorly understood. Here, we demonstrate that DRT4, a single-gene anti-phage defense system, synthesizes single-stranded DNA (ssDNA) products of random sequences in a template-independent manner. High-resolution cryo-EM structures of DRT4 in multiple functional states elucidate its oligomeric architecture, catalytic metal ion coordination, and substrate/DNA product binding, offering mechanistic insights into its promiscuous polymerization activity. Structural and biochemical analyses further identify a conserved tyrosine residue that acts as the priming site for the initiation of DNA synthesis.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12783706 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature