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- Title
Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1.
- Authors
Di Giovine, Paolo; Settembre, Ethan C.; Bhargava, Arjun K.; Luftig, Micah A.; Lou, Huan; Cohen, Gary H.; Eisenberg, Roselyn J.; Krummenacher, Claude; Carfi, Andrea
- Abstract
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 Igdomain 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.
- Subjects
HERPES simplex virus; GLYCOPROTEINS; CELL membranes; MEMBRANE fusion; CELLS
- Publication
PLoS Pathogens, 2011, Vol 7, Issue 9, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1002277