A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity

Lawrence H. Pinto; Gregg R. Dieckmann; Chris S. Gandhi; Carol G. Papworth; Jeffrey Braman; Margaret A. Shaughnessy; James D. Lear; Robert A. Lamb; William F. Degrado

doi:10.1073/pnas.94.21.11301

A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity

Lawrence H. Pinto^*, Gregg R. Dieckmann, Chris S. Gandhi, Carol G. Papworth, Jeffrey Braman, Margaret A. Shaughnessy, James D. Lear, Robert A. Lamb, William F. Degrado

^*Corresponding author for this work

Molecular Biosciences

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111 Scopus citations

Abstract

The M₂ protein from influenza A virus forms proton-selective channels that are essential to viral function and are the target of the drug amantadine. Cys scanning was used to generate a series of mutants with successive substitutions in the transmembrane segment of the protein, and the mutants were expressed in Xenopus laevis oocytes. The effect of the mutations on reversal potential, ion currents, and amantadine resistance were measured. Fourier analysis revealed a periodicity consistent with a four-stranded coiled coil or helical bundle. A three-dimensional model of this structure suggests a possible mechanism for the proton selectivity of the M₂ channel of influenza virus.

Original language	English (US)
Pages (from-to)	11301-11306
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	94
Issue number	21
DOIs	https://doi.org/10.1073/pnas.94.21.11301
State	Published - Oct 14 1997

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Pinto, L. H., Dieckmann, G. R., Gandhi, C. S., Papworth, C. G., Braman, J., Shaughnessy, M. A., Lear, J. D., Lamb, R. A., & Degrado, W. F. (1997). A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity. Proceedings of the National Academy of Sciences of the United States of America, 94(21), 11301-11306. https://doi.org/10.1073/pnas.94.21.11301

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title = "A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity",

abstract = "The M2 protein from influenza A virus forms proton-selective channels that are essential to viral function and are the target of the drug amantadine. Cys scanning was used to generate a series of mutants with successive substitutions in the transmembrane segment of the protein, and the mutants were expressed in Xenopus laevis oocytes. The effect of the mutations on reversal potential, ion currents, and amantadine resistance were measured. Fourier analysis revealed a periodicity consistent with a four-stranded coiled coil or helical bundle. A three-dimensional model of this structure suggests a possible mechanism for the proton selectivity of the M2 channel of influenza virus.",

author = "Pinto, {Lawrence H.} and Dieckmann, {Gregg R.} and Gandhi, {Chris S.} and Papworth, {Carol G.} and Jeffrey Braman and Shaughnessy, {Margaret A.} and Lear, {James D.} and Lamb, {Robert A.} and Degrado, {William F.}",

year = "1997",

month = oct,

day = "14",

doi = "10.1073/pnas.94.21.11301",

language = "English (US)",

volume = "94",

pages = "11301--11306",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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publisher = "National Academy of Sciences",

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Pinto, LH, Dieckmann, GR, Gandhi, CS, Papworth, CG, Braman, J, Shaughnessy, MA, Lear, JD, Lamb, RA & Degrado, WF 1997, 'A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity', Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 21, pp. 11301-11306. https://doi.org/10.1073/pnas.94.21.11301

A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity. / Pinto, Lawrence H.; Dieckmann, Gregg R.; Gandhi, Chris S. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 21, 14.10.1997, p. 11301-11306.

Research output: Contribution to journal › Article › peer-review

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T1 - A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity

AU - Pinto, Lawrence H.

AU - Dieckmann, Gregg R.

AU - Gandhi, Chris S.

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AU - Braman, Jeffrey

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AU - Lear, James D.

AU - Lamb, Robert A.

AU - Degrado, William F.

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A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity

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