Herpes simplex virus glycoprotein D bound to the human receptor HveA

Herpes simplex virus (HSV) infection requires binding of the viral envelope glycoprotein D (gD) to cell surface receptors. We report the X-ray structu res of a soluble, truncated ectodomain of go both alone and in complex with the ectodomain of its cellular receptor HveA. Two bound anions suggest pos sible binding sites for another go receptor, a 3-O-sulfonated heparan sulfa te. Unexpectedly, the structures reveal a V-like immunoglobulin tig) fold a t the core of go that is closely related to cellular adhesion molecules and flanked by large N- and C-terminal extensions. The receptor binding segmen t of gD, an N-terminal hairpin, appears conformationally flexible, suggesti ng that a conformational change accompanying binding might be part of the v iral entry mechanism.