Structure of an antibody in complex with its mucin domain linear epitope that is protective against Ebola virus

J Virol. 2012 Mar;86(5):2809-16. doi: 10.1128/JVI.05549-11. Epub 2011 Dec 14.

Abstract

Antibody 14G7 is protective against lethal Ebola virus challenge and recognizes a distinct linear epitope in the prominent mucin-like domain of the Ebola virus glycoprotein GP. The structure of 14G7 in complex with its linear peptide epitope has now been determined to 2.8 Å. The structure shows that this GP sequence forms a tandem β-hairpin structure that binds deeply into a cleft in the antibody-combining site. A key threonine at the apex of one turn is critical for antibody interaction and is conserved among all Ebola viruses. This work provides further insight into the mechanism of protection by antibodies that target the protruding, highly accessible mucin-like domain of Ebola virus and the structural framework for understanding and characterizing candidate immunotherapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / chemistry*
  • Antibodies, Viral / immunology*
  • Binding Sites, Antibody
  • Ebolavirus / chemistry
  • Ebolavirus / genetics
  • Ebolavirus / immunology*
  • Hemorrhagic Fever, Ebola / immunology
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Hemorrhagic Fever, Ebola / virology
  • Humans
  • Inverted Repeat Sequences
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • Antibodies, Viral
  • Viral Envelope Proteins
  • envelope glycoprotein, Ebola virus

Associated data

  • PDB/2Y6S