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Backbone Structure of the Amantadine-Blocked Trans-Membrane Domain M2 Proton Channel from Influenza A Virus

by Hu, Jun , Li, Conggang , Asbury, Tom , Bertram, Richard , Quine, Jack R. , Achuthan, Srisairam , Cross, Timothy A. , Fu, Riqiang

in Amantadine - chemistry / Antiviral drugs / Cell Membrane - chemistry / Channels, Receptors, and Electrical Signaling / Computer Simulation / Influenza / Influenza A virus / Ion Channel Gating / Magnetic Resonance Spectroscopy / Membranes / Models, Chemical / Models, Molecular / Protein Conformation / Protein Structure, Tertiary / Protons / Viral Matrix Proteins - chemistry / Viral Matrix Proteins - ultrastructure

2007

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Backbone Structure of the Amantadine-Blocked Trans-Membrane Domain M2 Proton Channel from Influenza A Virus

by Hu, Jun , Li, Conggang , Asbury, Tom , Bertram, Richard , Quine, Jack R. , Achuthan, Srisairam , Cross, Timothy A. , Fu, Riqiang

2007

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Backbone Structure of the Amantadine-Blocked Trans-Membrane Domain M2 Proton Channel from Influenza A Virus

by Hu, Jun , Li, Conggang , Asbury, Tom , Bertram, Richard , Quine, Jack R. , Achuthan, Srisairam , Cross, Timothy A. , Fu, Riqiang

2007

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Journal Article

Backbone Structure of the Amantadine-Blocked Trans-Membrane Domain M2 Proton Channel from Influenza A Virus

Hu, Jun,

Li, Conggang,

Asbury, Tom,

Bertram, Richard,

Quine, Jack R.,

Achuthan, Srisairam,

Cross, Timothy A.,

Fu, Riqiang

2007

Overview

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° and 31° 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.

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Publisher

Elsevier Inc,Biophysical Society

Subject

Amantadine - chemistry

/ Antiviral drugs

/ Cell Membrane - chemistry

/ Channels, Receptors, and Electrical Signaling

/ Computer Simulation

/ Influenza

/ Influenza A virus