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

(2015) JOURNAL OF VIROLOGY. 89(7). p.3700-3711
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Abstract
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 angstrom 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.
Keywords
ECTODOMAIN, MECHANISM, IN-VIVO, IMMUNOGENIC PEPTIDE, SOLUTION CONFORMATION, PROTON CHANNEL, M2 PROTEIN, NMR, HEMAGGLUTININ, REPLICATION

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Chicago
Cho, Ki Joon, Bert Schepens, Jong Hyeon Seok, Sella Kim, Kenny Roose, Ji-Hye Lee, Rodrigo Gallardo, et al. 2015. “Structure of the Extracellular Domain of Matrix Protein 2 of Influenza A Virus in Complex with a Protective Monoclonal Antibody.” Journal of Virology 89 (7): 3700–3711.
APA
Cho, K. J., Schepens, B., Seok, J. H., Kim, S., Roose, K., Lee, J.-H., Gallardo, R., et al. (2015). Structure of the extracellular domain of matrix protein 2 of influenza A virus in complex with a protective monoclonal antibody. JOURNAL OF VIROLOGY, 89(7), 3700–3711.
Vancouver
1.
Cho KJ, Schepens B, Seok JH, Kim S, Roose K, Lee J-H, et al. Structure of the extracellular domain of matrix protein 2 of influenza A virus in complex with a protective monoclonal antibody. JOURNAL OF VIROLOGY. 2015;89(7):3700–11.
MLA
Cho, Ki Joon, Bert Schepens, Jong Hyeon Seok, et al. “Structure of the Extracellular Domain of Matrix Protein 2 of Influenza A Virus in Complex with a Protective Monoclonal Antibody.” JOURNAL OF VIROLOGY 89.7 (2015): 3700–3711. Print.
@article{5951649,
  abstract     = {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 angstrom 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.},
  author       = {Cho, Ki Joon and Schepens, Bert and Seok, Jong Hyeon and Kim, Sella and Roose, Kenny and Lee, Ji-Hye and Gallardo, Rodrigo and Van Hamme, Evelien and Schymkowitz, Joost and Rousseau, Frederic and Fiers, Walter and Saelens, Xavier and Kim, Kyung Hyun},
  issn         = {0022-538X},
  journal      = {JOURNAL OF VIROLOGY},
  keyword      = {ECTODOMAIN,MECHANISM,IN-VIVO,IMMUNOGENIC PEPTIDE,SOLUTION CONFORMATION,PROTON CHANNEL,M2 PROTEIN,NMR,HEMAGGLUTININ,REPLICATION},
  language     = {eng},
  number       = {7},
  pages        = {3700--3711},
  title        = {Structure of the extracellular domain of matrix protein 2 of influenza A virus in complex with a protective monoclonal antibody},
  url          = {http://dx.doi.org/10.1128/JVI.02576-14},
  volume       = {89},
  year         = {2015},
}

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