title: Membrane-proximal cytoplasmic domain of Moloney murine leukemia virus envelope tail facilitates fusion.
abstract: Removal of the R peptide (residues 617-632) from the Moloney murine leukemia virus (MoMuLV) envelope protein (Env) cytoplasmic tail potentiates fusion. We examined the role of the membrane-proximal cytoplasmic domain (598-616) of the MoMuLV Env in the Env-mediated membrane fusion and incorporation. The Env truncated at 616 exhibits maximum fusogenicity in cell-to-cell fusion assay. By comparison, full tail Env (632) and the Env truncated to residue 601 mediated fusion at 40%. The Envs truncated to residues 598 or 595 are not fusogenic. Progressive cytoplasmic tail truncation correlated with decreased Env incorporation into virions. Substitution of the domain 598-616 with an amphiphilic alpha-helix from melittin results in maximally fusogenic Envs that efficiently incorporated into transduction competent virions. However, substitution of the domain 598-616 with random or hydrophilic sequences caused loss of the Env fusogenicity and titer while retaining incorporation. Further, a secondary structure prediction analysis of 27 unrelated Env cytoplasmic tails indicates a common (23/27) propensity for an amphiphilic alpha-helical domain at immediate proximity to the viral membrane. These results support the suggestion that viral fusion is enhanced by a membrane-proximal cytoplasmic amphiphilic alpha-helix in Env tail. The model of its action is proposed.
authors.affiliation: San Diego Cancer Research Institute, 1200 Garden View, Suite 200, Encinitas, CA 92024, USA. YaninaAdler@cox.net
authors.forename: Yanina
authors.initials: Y
authors.lastname: Rozenberg-Adler
authors.forename: John
authors.initials: J
authors.lastname: Conner
authors.forename: Hector
authors.initials: H
authors.lastname: Aguilar-Carreno
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
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D015686:Gene Products, env / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008555:Melitten / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015686:Gene Products, env; D011993:Recombinant Fusion Proteins; D008555:Melitten