Influence of extracellular and cytoplasmic domains of M2 ion channel of influenza a virus on its activity.
Co-expression of M2 protein of Influenza A virus (IAV) with pH-sensitive hemagglutinin (HA) reduces the conversion of HA to its low pH conformation during transport to the cell surface. Mutational analysis of extracellular domain of M2 protein showed that single aa substitution W 15A did not influence the ion channel activity of M2 protein. Replacement of first 24 aa of M2 protein with first 18 aa of NB protein of Influenza B virus in chimera BAA resulted in the loss of ion channel activity. The chimera B(SSD)AA had only first 21 aa replaced with first 18 aa of NB protein The remaining aa at positions 22, 23, and 24 were preserved from the wtM2 protein. The ion channel activity of B(SSD)AA chimera was fully restored and showed that the aa S22, S23, and D24 from wtM2 were important for the ion channel activity. However, these aa did not contribute to the activity of M2 protein directly, since they could be substituted by A, R, or H without change in ion channel activity. Mutational analysis of cytoplasmic domain of M2 protein showed that substitutions C50S, C50P, and H90S did not change the ion channel activity. The extracellular and cytoplasmic domains of M2 protein were not essential for ion channel activity of M2 protein.
Kollerova
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Institute of Virology, Slovak Academy of Sciences, 84505 Bratislava, Slovak Republic.
Betakova
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D002460:Cell Line; D004252:DNA Mutational Analysis; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000086082:Viroporin Proteins
D007473:Ion Channels; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins