Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1.

Published

Journal Article

Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 Å resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting β-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region.

Full Text

Duke Authors

Cited Authors

  • Di Giovine, P; Settembre, EC; Bhargava, AK; Luftig, MA; Lou, H; Cohen, GH; Eisenberg, RJ; Krummenacher, C; Carfi, A

Published Date

  • September 2011

Published In

Volume / Issue

  • 7 / 9

Start / End Page

  • e1002277 -

PubMed ID

  • 21980294

Pubmed Central ID

  • 21980294

Electronic International Standard Serial Number (EISSN)

  • 1553-7374

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1002277

Language

  • eng

Conference Location

  • United States