Abstract
This chapter summarizes and evaluates the evidence that the M2 proteins of influenza A and B viruses possess intrinsic ion channel activity that is essential to the life cycle of the virus. Both of these proteins are homotetramers with fewer than 100 residues per subunit, an N-terminal ectodomain and a single transmembrane (TM) domain. There is little amino acid homology between the two proteins other than a H-X-X-X-W motif in the TM domain. The proton selectivity of the A/M2 ion channel depends on the presence of a TM domain histidine residue, which serves as a “selectivity filter.” It is possible that this filter functions by binding protons and subsequently releasing them to the opposite side of the TM pore. Protons normally flow from the acidic medium bathing the ectodomain of the protein through the TM pore and then into the virion interior. Protons are prevented from flowing through the pore of the A/M2 channel in the opposite direction by a TM tryptophan residue, which serves as the activation “gate” that is closed if the medium bathing the ectodomain is neutral or alkaline. Thus, protons serve as both the activating stimulus and the conducted ion for the A/M2 channel. The BM2 protein has very little amino acid homology to the A/M2 protein, but it has ion channel activity that depends on TM histidine and tryptophan residues. Together, these proteins constitute the first-known members of the single-pass proton channel family.
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Tang, Y., Venkataraman, P., Knopman, J., Lamb, R.A., Pinto, L.H. (2005). The M2 Proteins of Influenza A and B Viruses are Single-Pass Proton Channels. In: Fischer, W.B. (eds) Viral Membrane Proteins: Structure, Function, and Drug Design. Protein Reviews, vol 1. Springer, Boston, MA. https://doi.org/10.1007/0-387-28146-0_8
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DOI: https://doi.org/10.1007/0-387-28146-0_8
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