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Matrix protein, M2, an acid activated drug-sensitive proton channel.  Transport involves binding to the four His-37s and transfer to water molecules on the inside of the channel (Acharya et al., 2010).  Functional properties and structure are known (Hong and Degrado 2012). The cytoplasmic tail facilitates proton conduction (Liao et al. 2015).  It is a dimer of dimers (Andreas et al. 2015).  The four TMSs flanking the channel lumen alone seem to determine the proton conduction mechanism (Liang et al. 2016). His-37 forms a planar tetrad in the configuration of the bundle accepting and translocating the incoming protons from the N terminal side, exterior of the virus, to the C terminal side, inside the virus (Kalita and Fischer 2017). The cholesterol binding site in M2 that mediates membrane scission in a cholesterol-dependent manner to cause virus budding and release has been identified (Elkins et al. 2017).Transport-related conformational changes coupled to water and H+ movements have been studied (Mandala et al. 2018). The L46P mutant confers a novel allosteric mechanism of resistance towards the influenza A virus M2 S31N proton channel blockers (Musharrafieh et al. 2019). The C-terminal domain of M2 may serve as a sensor that regulates how M2 participates in critical events in the viral infection cycle (Kim et al. 2019). The M2 proton channel protein  self-assembles into tetramers that retain the ability to bind to the drug amantadine, and the effects of phospholipid acyl chain length and cholesterol on the peptide association were investigated. Association of the helices depends on the thickness of the bilayer and cholesterol levels present in the phospholipid bilayer. The most favorable folding occurred when there was a good match between the width of the apolar region of the bilayer and the hydrophobic length of the transmembrane helix with tighter association upon inclusion of cholesterol in the lipid bilayer (Cristian et al. 2003).

Accession Number:P35938
Protein Name:VMT2 aka 7
Molecular Weight:11205.00
Species:Influenza A virus (strain A/USSR/90/77) [381516]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Virion membrane1 / Single-pass type III membrane protein2
Substrate hydron

Cross database links:

Pfam: PF00599   

Gene Ontology

GO:0020002 C:host cell plasma membrane
GO:0016021 C:integral to membrane
GO:0055036 C:virion membrane
GO:0015078 F:hydrogen ion transmembrane transporter acti...
GO:0005216 F:ion channel activity
GO:0015992 P:proton transport

References (5)

[1] “Primary structure of fragment 7 of the influenza virus A/USSR/90/77(H1N1) RNA.”  Samokhvalov   3877509
[2] “Assembly and budding of influenza virus.”  Nayak   15567494
[3] “Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data.”  Lear   12972146
[4] “Computational studies of proton transport through the M2 channel.”  Wu   12972147
[5] “The closed state of a H+ channel helical bundle combining precise orientational and distance restraints from solid state NMR.”  Nishimura   12403618
1NYJ   2H95     

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