The tryptophan 41 is not essential for the function of the M2 proton channel of influenza A virus

Abstract

The influenza A virus M2 protein as a proton-selective ion channel plays an important role in two steps of virus replication. Co-expression of the M2 protein with pH-sensitive HA reduces the conversion of HA to its low pH conformation during transport to the cell surface. Mutational analyses showed that replacement of Histidine 37 (His37) by Trp, Phe and Gln resulted in loss of activity. M2, with the mutation His37Ala, remained active but its severe toxicity is intolerable for cells. Whereas substitution of Ala for Trp 41 abolished detectable activity of the M2 channel, substitution of Leu resulted in a functional ion channel but with reduced activity. The activity of the Trp41Leu mutant M2, initially identified in a mutant virus, shows that the proposed role of tryptophan 41 in activation is not essential for functional activity.