The crystal structure of HSV-1 glycoprotein D bound to nectin-1 reveals that the nectin-1 binding site on gD differs from the HVEM receptor binding site, and mutation of nectin-1 Phe129 prevents gD binding and HSV entry.
The 4.0 Å crystal structure of HSV-1 gD bound to nectin-1 reveals the molecular interface required for viral entry and explains how gD disrupts nectin-1 homophilic cell adhesion.
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.
Giovine et al. (Thu,) conducted a other in Herpes Simplex Virus infection. Mutagenesis of nectin-1 and gD vs. Wild-type nectin-1 and gD was evaluated on Binding affinity and viral entry. The crystal structure of HSV-1 glycoprotein D bound to nectin-1 reveals that the nectin-1 binding site on gD differs from the HVEM receptor binding site, and mutation of nectin-1 Phe129 prevents gD binding and HSV entry.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: