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

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. © 2011 di giovine et al.