3SKU

Herpes simplex virus glycoprotein D bound to the human receptor nectin-1

Summary for 3SKU

• Entry DOI: 10.2210/pdb3sku/pdb
• Descriptor: Glycoprotein D, Poliovirus receptor-related protein 1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: immunoglobulin-like fold, viral protein-protein binding complex, viral protein/protein binding
• Biological source: Human herpesvirus 1 (HHV-1); More
• Total number of polymer chains: 6
• Total formula weight: 207072.96

Authors

Di Giovine, P.,Settembre, E.C.,Bhargava, A.K.,Luftig, M.A.,Lou, H.,Cohen, G.H.,Eisenberg, R.J.,Krummenacher, C.,Carfi, A. (deposition date: 2011-06-23, release date: 2011-10-12, Last modification date: 2024-11-06)

Primary citation

Di Giovine, P.,Settembre, E.C.,Bhargava, A.K.,Luftig, M.A.,Lou, H.,Cohen, G.H.,Eisenberg, R.J.,Krummenacher, C.,Carfi, A.
Structure of herpes simplex virus glycoprotein d bound to the human receptor nectin-1.
Plos Pathog., 7:e1002277-e1002277, 2011

PubMed 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.

PubMed: 21980294
DOI: 10.1371/journal.ppat.1002277

Experimental method

X-RAY DIFFRACTION (4 Å)