Membrane activity of an amphiphilic α-Helical membrane-proximal cytoplasmic domain of the MoMuLV envelope glycoprotein Academic Article uri icon

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  • In the Moloney murine leukemia virus (MoMuLV) envelope glycoprotein (Env) we identified a membrane-proximal cytoplasmic domain (residues 598-616) that facilitates the Env incorporation into virions and Env-mediated fusion [Rozenberg, Y., Conner, J., Aguilar-Carreno, H., Chakraborti, S., Dimiter, D.S., Anderson, W.F., 2008. Viral entry: membrane-proximal cytoplasmic domain of MoMuLV envelope tail facilitates fusion. In the same issue. (accompanying paper)]. By biophysical methods (CD, EPR) a corresponding peptide (membrane-proximal peptide, 598-616) was demonstrated to form a membrane-parallel amphiphilic alpha-helix in the presence of membranes. Electrophysiological studies with planar bilayers and liposomes indicate that the membrane-proximal peptide is membrane destabilizing. This peptide and the fusion peptide from the MoMuLV transmembrane (TM) ectodomain were tested for their effect on the bilayer for hexagonal phase transition temperature of dipalmitoleoylphosphatidylethanolamine (T(H)). Importantly, the external fusion peptide and the internal membrane-proximal peptides of MoMuLV env exert opposite effects on membrane curvature. The fusion peptide lowers T(H) while the membrane proximal peptide raises it. These effects on T(H) correlate with the ability of these peptides to induce lipid mixing in large unilamellar vesicles composed of dioleoylphosphatidylethanolamine: dioleoylphosphatidylcholine:cholesterol (1:1:1 mol). When added externally to preformed liposomes, the N-terminal fusion peptide promotes lipid mixing while the cytoplasmic membrane-proximal peptide inhibits this effect. These finding indicate a possible mechanism by which the membrane-proximal domain in MoMuLV Env may affect the formation of membrane fusion intermediates.


  • Epand, Raquel F
  • Zhang, Yan-Liang
  • Mirzabekov, Tajib
  • Kagan, Bruce
  • Silberstein, Anatoly
  • Hubbell, Wayne L
  • Epand, Richard
  • Chakraborti, Samitabh
  • Dimitrov, Dimiter S
  • Anderson, W French
  • Rozenberg-Adler, Yanina

publication date

  • February 2008