Amantadine blocks channel activity of the transmembrane segment of the NB protein from influenza B.
NB is short auxiliary protein with ca. 100 amino acids, encoded in the viral genome of influenza B. It is believed to be similar to M2 from influenza A and Vpu from HIV-1 in that it demonstrates ion channel activity. Channels formed by the protein can be blocked by amantadine. We have synthesized the putative transmembrane segment of NB (IRG S20 IIITICVSL I30 VILIVFGCI A40 KIFI (NB, Lee)). Reconstituted in a lipid bilayer, the peptide shows channel activity. The addition of amantadine leads to dose-dependent loss of channel activity. Channel blocking is reversible. Channel behaviour of the peptide in the presence of amantadine is in accordance with findings for the intact channel. Thus, the synthetic transmembrane peptide captures the ion channel activity of the intact NB protein.
Fischer
W B
WB
Department of Biochemistry, University of Oxford, UK. wolfgang@bioch.ox.ac.uk
Pitkeathly
M
M
Sansom
M S
MS
D000547:Amantadine / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D055592:Biophysical Phenomena; D001703:Biophysics; D002462:Cell Membrane / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D016679:Genome, Viral; D009981:Influenza B virus / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D017434:Protein Structure, Tertiary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014764:Viral Proteins / Q000737:chemistry*
D000998:Antiviral Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D008055:Lipids; C051094:NB glycoprotein, Influenza B virus; D014764:Viral Proteins; D000547:Amantadine