Structure of a core fragment of glycoprotein H from pseudorabies virus in complex with antibody

Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22635-40. doi: 10.1073/pnas.1011507107. Epub 2010 Dec 13.

Abstract

Compared with many well-studied enveloped viruses, herpesviruses use a more sophisticated molecular machinery to induce fusion of viral and cellular membranes during cell invasion. This essential function is carried out by glycoprotein B (gB), a class III viral fusion protein, together with the heterodimer of glycoproteins H and L (gH/gL). In pseudorabies virus (PrV), a porcine herpesvirus, it was shown that gH/gL can be substituted by a chimeric fusion protein gDgH, containing the receptor binding domain (RBD) of glycoprotein D fused to a truncated version of gH lacking its N-terminal domain. We report here the 2.1-Å resolution structure of the core fragment of gH present in this chimera, bound to the Fab fragment of a PrV gH-specific monoclonal antibody. The structure strongly complements the information derived from the recently reported structure of gH/gL from herpes simplex virus type 2 (HSV-2). Together with the structure of Epstein-Barr virus (EBV) gH/gL reported in parallel, it provides insight into potentially functional conserved structural features. One feature is the presence of a syntaxin motif, and the other is an extended "flap" masking a conserved hydrophobic patch in the C-terminal domain, which is closest to the viral membrane. The negative electrostatic surface potential of this domain suggests repulsive interactions with the lipid heads. The structure indicates the possible unmasking of an extended hydrophobic patch by movement of the flap during a receptor-triggered conformational change of gH, exposing a hydrophobic surface to interact with the viral membrane during the fusion process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Binding Sites / genetics
  • Cell Line
  • Crystallization
  • Herpesvirus 1, Suid / genetics
  • Herpesvirus 1, Suid / metabolism
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fab Fragments / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Protein Structure, Tertiary*
  • Sequence Homology, Amino Acid
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics
  • Viral Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin Fab Fragments
  • Multiprotein Complexes
  • Viral Envelope Proteins
  • Viral Proteins
  • glycoprotein H, Suid Herpesvirus 1
  • glycoprotein L, Suid Herpesvirus 1

Associated data

  • PDB/2XQY