Structure of the extracellular domain of matrix protein 2 of influenza A virus in complex with a protective monoclonal antibody

J Virol. 2015 Apr;89(7):3700-11. doi: 10.1128/JVI.02576-14. Epub 2015 Jan 21.


The extracellular domain of influenza A virus matrix protein 2 (M2e) is conserved and is being evaluated as a quasiuniversal influenza A vaccine candidate. We describe the crystal structure at 1.6 Å resolution of M2e in complex with the Fab fragment of an M2e-specific monoclonal antibody that protects against influenza A virus challenge. This antibody binds M2 expressed on the surfaces of cells infected with influenza A virus. Five out of six complementary determining regions interact with M2e, and three highly conserved M2e residues are critical for this interaction. In this complex, M2e adopts a compact U-shaped conformation stabilized in the center by the highly conserved tryptophan residue in M2e. This is the first description of the three-dimensional structure of M2e.

Importance: M2e of influenza A is under investigation as a universal influenza A vaccine, but its three-dimensional structure is unknown. We describe the structure of M2e stabilized with an M2e-specific monoclonal antibody that recognizes natural M2. We found that the conserved tryptophan is positioned in the center of the U-shaped structure of M2e and stabilizes its conformation. The structure also explains why previously reported in vivo escape viruses, selected with a similar monoclonal antibody, carried proline residue substitutions at position 10 in M2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / isolation & purification
  • Antibodies, Viral / metabolism
  • Crystallography, X-Ray
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / isolation & purification
  • Immunoglobulin Fab Fragments / metabolism
  • Mice, Inbred BALB C
  • Protein Binding
  • Protein Conformation
  • Viral Matrix Proteins / chemistry*


  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Immunoglobulin Fab Fragments
  • M2 protein, Influenza A virus
  • Viral Matrix Proteins

Associated data

  • PDB/4N8C