The C-terminal domain of TolA is the coreceptor for filamentous phage infection of E. coli.

Filamentous bacteriophages infecting gram-negative bacteria display tropism for a variety of pilus structures. However, the obligatory coreceptor of phage infection, postulated from genetic studies, has remained elusive. Here we identify the C-terminal domain of the periplasmic protein TolA as the coreceptor for infection of Escherichia coli by phage fd and the N-terminal domain of the phage minor coat protein g3p as its cognate ligand. The neighboring g3p domain binds the primary receptor of phage infection, the F pilus, and blocks TolA binding in its absence. Contact with the pilus releases this blockage during infection. Our findings support a sequential two-way docking mechanism for phage infection, analogous to infection pathways proposed for a range of eukaryotic viruses including herpes simplex, adenoviruses, and also lentiviruses like HIV-1.