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Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from Influenza A virus.

ABSTRACT: Amantadine is known to block the M2 proton channel of the Influenza A virus. Here, we present a structure of the M2 trans-membrane domain blocked with amantadine, built using orientational constraints obtained from solid-state NMR polarization-inversion-spin-exchange-at-the-magic-angle experiments. The data indicates a kink in the monomer between two helical fragments having 20 degrees and 31 degrees tilt angles with respect to the membrane normal. This monomer structure is then used to construct a plausible model of the tetrameric amantadine-blocked M2 trans-membrane channel. The influence of amantadine binding through comparative cross polarization magic-angle spinning spectra was also observed. In addition, spectra are shown of the amantadine-resistant mutant, S31N, in the presence and absence of amantadine.

SUBMITTER: Hu J

PROVIDER: S-EPMC1877758 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from Influenza A virus.

Hu Jun J Asbury Tom T Achuthan Srisairam S Li Conggang C Bertram Richard R Quine Jack R JR Fu Riqiang R Cross Timothy A TA

Biophysical journal 20070323 12

Amantadine is known to block the M2 proton channel of the Influenza A virus. Here, we present a structure of the M2 trans-membrane domain blocked with amantadine, built using orientational constraints obtained from solid-state NMR polarization-inversion-spin-exchange-at-the-magic-angle experiments. The data indicates a kink in the monomer between two helical fragments having 20 degrees and 31 degrees tilt angles with respect to the membrane normal. This monomer structure is then used to construc ...[more]

PMID: 17384070

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