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Kinetics of proton transport into influenza virions by the viral M2 channel

Journal Article


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Abstract


  • M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed an in vitro fluorescence-based assay to monitor internal acidification of individual virions triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of M2 proton conductance, blocks the acidification-dependent dissipation of fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation usually follows internal acidification but does not require it. The rate of internal virion acidification increases with external proton concentration and saturates with a pKm of ~4.7. The rate of proton transport through a single, fully protonated M2 channel is approximately 100 to 400 protons per second. The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer.

Authors


  •   Ivanovic, Tijana (external author)
  •   Rozendaal, Rutgre (external author)
  •   Floyd, Daniel L. (external author)
  •   Popovic, Milos (external author)
  •   van Oijen, Antoine M.
  •   Harrison, Stephen C. (external author)

Publication Date


  • 2012

Citation


  • Ivanovic, T., Rozendaal, R., Floyd, D. L., Popovic, M., van Oijen, A. M. & Harrison, S. C. (2012). Kinetics of proton transport into influenza virions by the viral M2 channel. PLoS One, 7 (3), e31566-1-e31566-9.

Scopus Eid


  • 2-s2.0-84857871573

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3189&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2171

Has Global Citation Frequency


Start Page


  • e31566-1

End Page


  • e31566-9

Volume


  • 7

Issue


  • 3

Place Of Publication


  • United States

Abstract


  • M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed an in vitro fluorescence-based assay to monitor internal acidification of individual virions triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of M2 proton conductance, blocks the acidification-dependent dissipation of fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation usually follows internal acidification but does not require it. The rate of internal virion acidification increases with external proton concentration and saturates with a pKm of ~4.7. The rate of proton transport through a single, fully protonated M2 channel is approximately 100 to 400 protons per second. The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer.

Authors


  •   Ivanovic, Tijana (external author)
  •   Rozendaal, Rutgre (external author)
  •   Floyd, Daniel L. (external author)
  •   Popovic, Milos (external author)
  •   van Oijen, Antoine M.
  •   Harrison, Stephen C. (external author)

Publication Date


  • 2012

Citation


  • Ivanovic, T., Rozendaal, R., Floyd, D. L., Popovic, M., van Oijen, A. M. & Harrison, S. C. (2012). Kinetics of proton transport into influenza virions by the viral M2 channel. PLoS One, 7 (3), e31566-1-e31566-9.

Scopus Eid


  • 2-s2.0-84857871573

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3189&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2171

Has Global Citation Frequency


Start Page


  • e31566-1

End Page


  • e31566-9

Volume


  • 7

Issue


  • 3

Place Of Publication


  • United States