Structures of λ-like phage A8 tail tip bound to OmpC provide insight into receptor recognition

Bacteriophage infection begins with the specific recognition of bacterial surface receptors by tail tip proteins, a decisive event that determines host specificity and triggers genome delivery. However, the structural principles underlying this process remain poorly understood. Here, we determined high-resolution cryo-electron microscopy (cryo-EM) structures of the engineered λ-like bacteriophage A8 gpJ713 in the unbound form and bound to the outer membrane porin OmpC. Comparisons with our previously determined structures of wild-type λ gpJ alone and bound to LamB reveal conserved receptor binding-induced conformational transitions across λ-like siphoviruses, defining a general mechanistic framework for tail-tip recognition. Guided by this framework, we restored stable binding to the previously incompatible OmpC G40 variant and converted OmpF into a functional receptor through a minimal loop deletion. These proof-of-concept receptor reprogramming experiments demonstrate the predictive power of our structural model and illustrate how targeted receptor engineering can complement directed evolution in developing therapeutic phages.