tetano
Editor, Senior Moderator
J Virol. 2015 Jan 21. pii: JVI.02576-14. [Epub ahead of print]
[h=1]Structure of the Extracellular Domain of Matrix Protein 2 of Influenza A Virus in Complex with a Protective Monoclonal Antibody.[/h] Cho KJ[SUP]1[/SUP], Schepens B[SUP]2[/SUP], Seok JH[SUP]3[/SUP], Kim S[SUP]3[/SUP], Roose K[SUP]2[/SUP], Lee JH[SUP]3[/SUP], Gallardo R[SUP]4[/SUP], Hamme EV[SUP]2[/SUP], Schymkowitz J[SUP]4[/SUP], Rousseau F[SUP]4[/SUP], Fiers W[SUP]2[/SUP], Saelens X[SUP]5[/SUP], Kim KH[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The extracellular domain of influenza A virus matrix protein 2 (M2, M2e) is conserved and is being evaluated as a quasi-universal influenza A vaccine candidate. We describe the crystal structure at 1.6 ? 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 surface 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 centre by the highly conserved tryptophan residue in M2e. This is the first description of the three dimensional structure of M2e.
[h=4]IMPORTANCE:[/h] 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 centre 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.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25609808 [PubMed - as supplied by publisher]
[h=1]Structure of the Extracellular Domain of Matrix Protein 2 of Influenza A Virus in Complex with a Protective Monoclonal Antibody.[/h] Cho KJ[SUP]1[/SUP], Schepens B[SUP]2[/SUP], Seok JH[SUP]3[/SUP], Kim S[SUP]3[/SUP], Roose K[SUP]2[/SUP], Lee JH[SUP]3[/SUP], Gallardo R[SUP]4[/SUP], Hamme EV[SUP]2[/SUP], Schymkowitz J[SUP]4[/SUP], Rousseau F[SUP]4[/SUP], Fiers W[SUP]2[/SUP], Saelens X[SUP]5[/SUP], Kim KH[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The extracellular domain of influenza A virus matrix protein 2 (M2, M2e) is conserved and is being evaluated as a quasi-universal influenza A vaccine candidate. We describe the crystal structure at 1.6 ? 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 surface 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 centre by the highly conserved tryptophan residue in M2e. This is the first description of the three dimensional structure of M2e.
[h=4]IMPORTANCE:[/h] 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 centre 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.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25609808 [PubMed - as supplied by publisher]