M2 amphipathic helices facilitate pH-dependent conformational transition in influenza A virus
Hedieh Torabifard, Afra Panahi, Charles L. Brooks
Abstract
Significance The influenza M2 protein is an integral membrane protein that transports protons across the viral envelope upon acid activation. M2 has become the target of numerous experimental and theoretical studies due to its important role in flu infection; however, there are still unresolved questions regarding the proton-conductance mechanism. In addition, these studies were mostly performed on constructs containing only the TM domain of the protein. We have applied explicit solvent CpHMD MSλD to the M2 construct containing the TM and AH domains, as well as the truncated M2. Our model provides a qualitative picture of pH-dependent conformational transitions in the M2 channel that suggests an important role of the AH on this transition and, consequently, on the proton-transport mechanism.