Structure and Mechanism of the M2 Channel
James J. Chou and Jason R. Schnell
from: Influenza: Molecular Virology (Edited by: Qinghua Wang and Yizhi Jane Tao). Caister Academic Press, U.K. (2010)
Viral ion channels have minimalist architecture. Despite their relatively simple structure, viral channels can achieve highly specific gating and selection of ions, and the particular mechanisms appear to be different from those of prokaryotes and eukaryotes. The unique structural and functional properties of viral channels make them ideal targets for antiviral therapy because the molecules that inhibit viral ion channels may not interact with human ion channels. The M2 proton channel of influenza A virus is a model viral ion channel. This small channel, whose pore is formed by four equivalent transmembrane helices, is the target of two widely used anti-influenza A drugs, amantadine and rimantadine, both belonging to the adamantane class of compounds. However, resistance of influenza A to adamantane is now widespread. Naturally-occurring resistants mutants have been observed in as many as six different positions in the transmembrane segment of M2. How could there be so many different resistance-conferring mutations along a transmembrane helix of 25 amino acids? The recently-determined high-resolution structures of M2 in complex with adamantane allow us to begin answering this question read more ...