Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR

Binding of virus particles to specific host cell surface receptors is known to be an obligatory step in infection even though the molecular basis for these interactions is not well characterized. The crystal structure of the adenovirus fiber knob domain in complex with domain I of its human cellular receptor, coxsackie and adenovirus receptor (CAR), is presented here. Surf ace-exposed Loops on knob contact one face of CAR, forming a high-affinity complex. Topology mismatches between interacting surfaces create interfacia l solvent-filled cavities and channels that may be targets for antiviral dr ug therapy. The structure identifies key determinants of binding specificit y, which may suggest ways to modify the tropism of adenovirus-based gene th erapy vectors.