Asp44 stabilizes the Trp41 gate of the M2 proton channel of influenza a virus

Chunlong Ma, Giacomo Fiorin, Vincenzo Carnevale, Jun Wang, Robert A. Lamb, Michael L. Klein, Yibing Wu, Lawrence H. Pinto, William F. Degrado

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Channel gating and proton conductance of the influenza A virus M2 channel result from complex pH-dependent interactions involving the pore-lining residues His37, Trp41, and Asp44. Protons diffusing from the outside of the virus protonate His37, which opens the Trp41 gate and allows one or more protons to move into the virus interior. The Trp41 gate gives rise to a strong asymmetry in the conductance, favoring rapid proton flux only when the outside is at acid pH. Here, we show that the proton currents recorded for mutants of Asp44, including D44N found in the A/FPV/Rostock/34 strain, lose this asymmetry. Moreover, NMR and MD simulations show that the mutations induce a conformational change similar to that induced by protonation of His37 at low pH, and decrease the structural stability of the hydrophobic seal associated with the Trp41 gate. Thus, Asp44 is able to determine two important properties of the M2 proton channel.

Original languageEnglish (US)
Pages (from-to)2033-2041
Number of pages9
JournalStructure
Volume21
Issue number11
DOIs
StatePublished - Nov 5 2013
Externally publishedYes

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Orthomyxoviridae
Protons
Viruses
Influenza A virus
Mutation
Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Ma, C., Fiorin, G., Carnevale, V., Wang, J., Lamb, R. A., Klein, M. L., ... Degrado, W. F. (2013). Asp44 stabilizes the Trp41 gate of the M2 proton channel of influenza a virus. Structure, 21(11), 2033-2041. https://doi.org/10.1016/j.str.2013.08.029

Asp44 stabilizes the Trp41 gate of the M2 proton channel of influenza a virus. / Ma, Chunlong; Fiorin, Giacomo; Carnevale, Vincenzo; Wang, Jun; Lamb, Robert A.; Klein, Michael L.; Wu, Yibing; Pinto, Lawrence H.; Degrado, William F.

In: Structure, Vol. 21, No. 11, 05.11.2013, p. 2033-2041.

Research output: Contribution to journalArticle

Ma, C, Fiorin, G, Carnevale, V, Wang, J, Lamb, RA, Klein, ML, Wu, Y, Pinto, LH & Degrado, WF 2013, 'Asp44 stabilizes the Trp41 gate of the M2 proton channel of influenza a virus', Structure, vol. 21, no. 11, pp. 2033-2041. https://doi.org/10.1016/j.str.2013.08.029
Ma, Chunlong ; Fiorin, Giacomo ; Carnevale, Vincenzo ; Wang, Jun ; Lamb, Robert A. ; Klein, Michael L. ; Wu, Yibing ; Pinto, Lawrence H. ; Degrado, William F. / Asp44 stabilizes the Trp41 gate of the M2 proton channel of influenza a virus. In: Structure. 2013 ; Vol. 21, No. 11. pp. 2033-2041.
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abstract = "Channel gating and proton conductance of the influenza A virus M2 channel result from complex pH-dependent interactions involving the pore-lining residues His37, Trp41, and Asp44. Protons diffusing from the outside of the virus protonate His37, which opens the Trp41 gate and allows one or more protons to move into the virus interior. The Trp41 gate gives rise to a strong asymmetry in the conductance, favoring rapid proton flux only when the outside is at acid pH. Here, we show that the proton currents recorded for mutants of Asp44, including D44N found in the A/FPV/Rostock/34 strain, lose this asymmetry. Moreover, NMR and MD simulations show that the mutations induce a conformational change similar to that induced by protonation of His37 at low pH, and decrease the structural stability of the hydrophobic seal associated with the Trp41 gate. Thus, Asp44 is able to determine two important properties of the M2 proton channel.",
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AU - Ma, Chunlong

AU - Fiorin, Giacomo

AU - Carnevale, Vincenzo

AU - Wang, Jun

AU - Lamb, Robert A.

AU - Klein, Michael L.

AU - Wu, Yibing

AU - Pinto, Lawrence H.

AU - Degrado, William F.

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AB - Channel gating and proton conductance of the influenza A virus M2 channel result from complex pH-dependent interactions involving the pore-lining residues His37, Trp41, and Asp44. Protons diffusing from the outside of the virus protonate His37, which opens the Trp41 gate and allows one or more protons to move into the virus interior. The Trp41 gate gives rise to a strong asymmetry in the conductance, favoring rapid proton flux only when the outside is at acid pH. Here, we show that the proton currents recorded for mutants of Asp44, including D44N found in the A/FPV/Rostock/34 strain, lose this asymmetry. Moreover, NMR and MD simulations show that the mutations induce a conformational change similar to that induced by protonation of His37 at low pH, and decrease the structural stability of the hydrophobic seal associated with the Trp41 gate. Thus, Asp44 is able to determine two important properties of the M2 proton channel.

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