Backbone Structure of the Amantadine-blocked Trans-membrane Domain M2 Proton Channel from Influenza A Virus

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2007 Mar 27

PMID 17384070

Citations 113

Authors

Jun Hu

Tom Asbury

Srisairam Achuthan

Conggang Li

Richard Bertram

Jack R Quine

Riqiang Fu

Timothy A Cross

Affiliations

Soon will be listed here.

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.

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