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