M2protonkanal

M2protonkanal, or the M2 proton channel, is a small, tetrameric transmembrane protein encoded by the M segment of influenza A virus. It forms a proton-selective channel in the viral envelope and in infected cell membranes, and its activity is essential for efficient viral replication. By allowing proton influx into the interior of the virion during endosomal acidification, M2 promotes uncoating and release of the viral ribonucleoprotein complexes into the host cell cytoplasm.

Structurally, each M2 subunit contributes a single transmembrane helix, and four subunits assemble to create a pore. The channel’s proton conductance is gated by histidine residues in the transmembrane region, particularly His37, with tryptophan 41 playing a role in stabilizing the closed state. Proton selectivity and gating depend on pH and the local environment, enabling the channel to respond to endosomal acidification. The mechanism involves a proton relay through water molecules and side-chain interactions within the pore.

Functionally, M2 activity facilitates uncoating by acidifying the virion interior after endocytosis, promoting dissociation of the matrix protein M1 from the viral ribonucleoprotein complexes. This step is a bottleneck in the viral lifecycle and thus a potential antiviral target. Influenza B uses a related protein called BM2, whereas M2 is specific to influenza A.

Inhibitors such as adamantanes (amantadine and rimantadine) block M2 pore conductance by binding within the channel. Widespread resistance, most notably the S31N substitution, has reduced clinical utility of these drugs. Consequently, M2-targeted antivirals are less prevalent, though ongoing research aims to identify novel inhibitors and strategies that circumvent resistance.