%0 Journal Article
%T Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1
%A Paolo Di Giovine equal contributor
%A Ethan C. Settembre equal contributor
%A Arjun K. Bhargava
%A Micah A. Luftig
%A Huan Lou
%A Gary H. Cohen
%A Roselyn J. Eisenberg
%A Claude Krummenacher
%A Andrea Carfi
%J PLOS Pathogens
%D 2011
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1002277
%X 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 £¿ 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 ¦Â-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.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002277