title: Herpes simplex virus glycoprotein D bound to the human receptor HveA.
abstract: Herpes simplex virus (HSV) infection requires binding of the viral envelope glycoprotein D (gD) to cell surface receptors. We report the X-ray structures of a soluble, truncated ectodomain of gD both alone and in complex with the ectodomain of its cellular receptor HveA. Two bound anions suggest possible binding sites for another gD receptor, a 3-O-sulfonated heparan sulfate. Unexpectedly, the structures reveal a V-like immunoglobulin (Ig) fold at the core of gD that is closely related to cellular adhesion molecules and flanked by large N- and C-terminal extensions. The receptor binding segment of gD, an N-terminal hairpin, appears conformationally flexible, suggesting that a conformational change accompanying binding might be part of the viral entry mechanism.
authors.affiliation: Department of Medicine, Children's Hospital, Howard Hughes Medical Institute, 320 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Carfí
authors.forename: S H
authors.initials: SH
authors.lastname: Willis
authors.forename: J C
authors.initials: JC
authors.lastname: Whitbeck
authors.forename: C
authors.initials: C
authors.lastname: Krummenacher
authors.forename: G H
authors.initials: GH
authors.lastname: Cohen
authors.forename: R J
authors.initials: RJ
authors.lastname: Eisenberg
authors.forename: D C
authors.initials: DC
authors.lastname: Wiley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D007477:Ions / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D007477:Ions; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1