Functional studies reveal the similarities and differences between AM2 and BM2 proton channels from influenza viruses

Chunlong Ma, Jun Wang

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

AM2 and BM2 proton channels are attractive antiviral drug targets due to their essential roles during influenza virus replication. Although both AM2 and BM2 are proton-selective ion channels, they share little sequence similarity except for the HXXXW sequence, which suggests that their proton conductance properties might differ. To test this hypothesis, we applied two-electrode voltage clamp electrophysiological assays to study the specific conductance, leakage current, channel activation, and inhibition of AM2 and BM2 proton channels. It was found that BM2 channel has a higher specific conductance than AM2 channel at pH 5.5. Unlike AM2 channel, whose proton conductance is asymmetric (from viral exterior to interior), BM2 channel is capable of conducting proton in both directions. Moreover, BM2 requires a more acidic pH for channel activation than AM2, as revealed by its lower pKa values. Finally, both AM2 and BM2 can be inhibited by Cu(II) and Cu(I). Overall, the results from this side-by-side comparison of AM2 and BM2 channels reveal the structure-function relationships of these two viroporins, and such information might be important for the designing of novel ion channels.

Original languageEnglish (US)
Pages (from-to)272-280
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1860
Issue number2
DOIs
StatePublished - Feb 1 2018

Keywords

  • AM2
  • BM2
  • Influenza viruses
  • Ion selectivity
  • Proton channel
  • Two-electrode voltage clamp

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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