Structural basis for DNA processing and membrane translocation by ComEC in natural transformation

Natural transformation is one of the major pathways of horizontal gene transfer in bacteria, enabling the acquisition of extracellular DNA and its integration into the host genome. ComEC is a membrane protein responsible for DNA translocation in this process, yet its precise function and structure have remained elusive. Here, we report cryo-electron microscopy structures of ComEC in DNA-free, single-stranded DNA (ssDNA)-bound, and double-stranded DNA (dsDNA)-bound forms, together with biochemical analyses. These structures reveal that ComEC cleaves one strand of dsDNA at its extracellular domain and guides the remaining strand into a positively charged pore formed within the membrane domain. These findings provide a structural basis for the long-hypothesized roles of ComEC in both DNA processing and translocation across the inner membrane during natural transformation.