The influenza virus ion channel and maturation cofactor M2 is a cholesterol-binding protein

European Biophysics Journal : EBJ
C SchroederT I Lin

Abstract

The influenza-virus M2 protein has proton channel activity required for virus uncoating and maturation of hemagglutinin (HA) through low-pH compartments. The proton channel is cytotoxic in heterologous expression systems and can be blocked with rimantadine. In an independent, rimantadine-resistant function, M2, interacting with the M1 protein, controls the shape of virus particles. These bud from cholesterol-rich membrane rafts where viral glycoproteins and matrix (M1)/RNP complexes assemble. We demonstrate that M2 preparations from influenza virus-infected cells and from a baculovirus expression system contain 0.5-0.9 molecules of cholesterol per monomer. Sequence analyses of the membrane-proximal M2 endodomain reveal interfacial hydrophobicity, a cholesterol-binding motif first identified in peripheral benzodiazepine receptor and human immunodeficiency virus gp41, and an overlapping phosphatidylinositol 4,5-bisphosphate-binding motif. M2 induced rimantadine-reversible cytotoxicity in intrinsically cholesterol-free E. coli, and purified E. coli-expressed M2 functionally reconstituted into cholesterol-free liposomes supported rimantadine-sensitive proton translocation. Therefore, cholesterol was nonessential for M2 ion-channel ...Continue Reading

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Citations

Sep 3, 2013·European Biophysics Journal : EBJ·Timothy A CrossAnthony Watts
Jun 2, 2011·Cold Spring Harbor Perspectives in Biology·Kai Simons, Julio L Sampaio
May 16, 2006·Journal of Virology·Kiyoko Iwatsuki-HorimotoYoshihiro Kawaoka
Mar 12, 2010·Journal of Virology·Jeremy S RossmanRobert A Lamb
Oct 9, 2013·Annual Review of Cell and Developmental Biology·Jeremy S Rossman, Robert A Lamb
Dec 23, 2011·Biochemistry Research International·Tadanobu Takahashi, Takashi Suzuki
Feb 9, 2012·Advances in Virology·Michael Veit, Bastian Thaa
Apr 14, 2012·Journal of Amino Acids·Megan E SchroederJudith M Ball
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Feb 17, 2017·Journal of Virology·George P Leser, Robert A Lamb

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