Stability and function of the influenza A virus M2 ion channel protein is determined by both extracellular and cytoplasmic domains.

A series of M2/NB chimeras were used to investigate the ion channel activity of the IAV M2 protein. Replacing the M2 cytoplasmic domain with the equivalent NB domain (AAB chimera) did not influence ion channel activity, while replacement of N-terminal domains (BAA and BAB chimeras) resulted in loss of activity. Extension of the M2 protein N-terminal domain resulted in full restoration of ion channel activity in BAA chimeras but only partial restoration in BAB. While not directly involved in ion channel activity, the N- and C-terminals of M2 are important for stabilization of the transmembrane domain structure.