title: Cytoplasmic tail of Moloney murine leukemia virus envelope protein influences the conformation of the extracellular domain: implications for mechanism of action of the R Peptide.
abstract: The envelope (Env) protein of Moloney murine leukemia virus (MoMuLV) is a homotrimeric complex whose monomers consist of linked surface (SU) and transmembrane (TM) proteins cleaved from a precursor protein by a cellular protease. In addition, a significant fraction of virion-associated TM is further processed by the viral protease to remove the C-terminal 16 amino acids of the cytoplasmic domain, the R peptide. This cleavage greatly enhances the fusogenicity of the protein and is necessary for the formation of a fully functional Env protein complex. We have previously proposed that R peptide cleavage enhances fusogenicity by altering the conformation of the ectodomain of the protein (Y. Zhao et al., J. Virol. 72:5392-5398, 1998). Using a series of truncation and point mutants of MoMuLV Env, we now provide direct biochemical and immunological evidence that the cytoplasmic tail and the membrane-spanning region of Env can influence the overall structure of the ectodomain of the protein and alter the strength of the SU-TM interaction. The R-peptide-truncated form of the protein, in particular, exhibits a markedly different conformation than the full-length protein.
authors.affiliation: Gene Therapy Laboratories, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA.
authors.forename: Hector C
authors.initials: HC
authors.lastname: Aguilar
authors.forename: W French
authors.initials: WF
authors.lastname: Anderson
authors.forename: Paula M
authors.initials: PM
authors.lastname: Cannon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000378:metabolism*; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014759:Viral Envelope Proteins