Abstract
The evidence presented shows that the M2 protein of influenza A viruses exists in infected cells as a homotetramer composed of two disulfide-linked dimers held together by noncovalent interactions. The amphiphilic nature of the transmembrane alpha-helical domain is consistent with the protein forming a transmembrane channel with which amantadine, the specific anti-influenza A drug, interacts. Together these features provide a structural basis for the hypothesis that M2 has a proton translocation function capable of regulating the pH of vesicles of the trans-Golgi network, a role important in promoting the correct maturation of the hemagglutinin glycoprotein.