title: Membrane activity of an amphiphilic alpha-helical membrane-proximal cytoplasmic domain of the MoMuLV envelope glycoprotein.
abstract: 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.
authors.affiliation: Department of Biochemistry, McMaster University Health Sciences Center, Hamilton, ON L8N 3Z5 Canada.
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Epand
authors.forename: Yan-Liang
authors.initials: YL
authors.lastname: Zhang
authors.forename: Tajib
authors.initials: T
authors.lastname: Mirzabekov
authors.forename: Bruce
authors.initials: B
authors.lastname: Kagan
authors.forename: Anatoly
authors.initials: A
authors.lastname: Silberstein
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Hubbell
authors.forename: Richard M
authors.initials: RM
authors.lastname: Epand
authors.forename: Samitabh
authors.initials: S
authors.lastname: Chakraborti
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
authors.forename: W French
authors.initials: WF
authors.lastname: Anderson
authors.forename: Yanina
authors.initials: Y
authors.lastname: Rozenberg-Adler
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D004594:Electrophysiology; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D053586:Virus Internalization
chemical_list: D015686:Gene Products, env; D008081:Liposomes; D010455:Peptides