Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion

Nat Commun. 2011 Dec 6;2:577. doi: 10.1038/ncomms1571.


Multiple surface envelope proteins are involved in the human herpes simplex virus type 1 entry and fusion. Among them, glycoprotein D (gD) has an important role by binding to the host receptors such as herpes virus entry mediator and nectin-1. Although the complex structure of gD with herpes virus entry mediator has been established, the binding mode of gD with the nectin-1 is elusive. Nectin-1 is a member of the immunoglobulin (Ig)-like (three Ig-like domains) cell adhesion molecules and is believed to form a homodimer to exert its functions. Here we report the complex structure of gD and nectin-1 (three Ig domains), revealing that gD binds the first Ig domain of nectin-1 in a similar mode to the nectin-1 homodimer interaction. The key amino acids responsible for nectin-1 dimerization are also used for gD/nectin-1 binding. This result indicates that binding of gD to nectin-1 would preclude the nectin-1 dimerization, consequently abolishing its cell adhesion function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Baculoviridae
  • Binding Sites
  • Cell Adhesion
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Dimerization
  • Escherichia coli
  • Herpes Simplex / metabolism*
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / chemistry
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / metabolism*
  • Humans
  • Models, Molecular
  • Nectins
  • Plasmids
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Virus / chemistry
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Virus Internalization*


  • Cell Adhesion Molecules
  • NECTIN1 protein, human
  • Nectins
  • Receptors, Virus
  • Recombinant Proteins
  • Viral Envelope Proteins
  • glycoprotein D, Human herpesvirus 1

Associated data

  • PDB/3U82
  • PDB/3U83