Scientists decode how bacteria fight viruses using a two-part molecular weapon
Researchers have mapped the structure and function of DRT7, a bacterial defense enzyme that works like a molecular assembly line to block viral infection. Understanding this mechanism could inform new strategies for biotech applications, from developing phage therapies to engineering more resilient microbial systems used in food production and industrial fermentation.
Originaltitel: Structures and enzymatic mechanisms of DRT7/UG10 antiphage reverse transcriptases
The ongoing evolutionary arms race between bacteria and bacteriophages has driven the emergence of numerous anti-phage defense systems. Several of these defenses contain domains related to reverse transcriptases (RTs), DNA polymerases that utilize RNA as a template. Certain members of the Abi/UG RT family employ a unique enzymatic mechanism combining protein-primed DNA synthesis with template-independent polymerization. A subgroup, UG10 - also known as Defense-related RT 7 (DRT7) - is characterized by an enzymatic core comprising an RT-like domain and a primase domain, accompanied by a poorly characterized accessory element. This element is either C-terminally fused to the core or encoded by a separate open reading frame. Here, we present cryo-EM structures of protein-DNA conjugates from two UG10 enzymes, revealing a compact yet flexible domain architecture. We demonstrate that the poly(dT) product synthesized by the RT-like domain serves as a template for the primase domain to generate a complementary poly(A) strand. Combining biochemical experiments with structural modeling, we propose the conformational changes necessary for protein priming and coordination between the RT and primase domains. Finally, we show that DRT7 exhibits broad-spectrum anti-phage activity and demonstrate that the λ phage DNA mimic protein Gam can trigger this defense system.