Matrix-2 protein of influenza A virus (M2 protein)

The **Matrix-2 (M2) protein of influenza A virus** is a small, 97-residue integral membrane protein that functions as a **proton-selective viroporin** (ion channel) embedded in the viral envelope[1][3][8]. As a homotetramer, it enables protons to enter the virion's interior in response to low pH in endosomes following viral entry. This acidification disrupts the association of viral ribonucleoproteins with the matrix protein, an essential step for viral uncoating and replication[3][6][8]. The channel is also required to regulate the pH in the trans-Golgi network, protecting viral proteins during assembly[3][8]. M2 is a prominent therapeutic target, especially for the adamantane class of antivirals (amantadine, rimantadine), but resistance mutations (notably S31N) are common, limiting their clinical effectiveness in modern influenza strains[2][4][8]. Structurally, the M2 protein consists of an extracellular N-terminal domain, a transmembrane helix that comprises the channel pore, and a C-terminal cytoplasmic tail involved in virus budding and assembly[1][8].

Other names

M2M2 proton channelAM2Influenza A M2 proteinMatrix-2M2 ion channel

Blockade of proton conductance by binding to the transmembrane domain, stabilizing the closed state of the channel and preventing acidification of the viral interior, which inhibits viral uncoating and replication[2][3][4][8].