title: The MuLV 4070A G541R Env mutation decreases the stability and alters the conformation of the TM ectodomain.
abstract: Virus-cell and cell-cell fusion events are affected by various properties of the fusogenic Env protein on the cell surface. The G541R mutation within the TM ectodomain of murine leukemia virus (MuLV) 4070A arose by positive selection in viral passage and results in a reduction of cell-cell fusion events while maintaining viral titer. Size exclusion chromatography shows that the multimerization properties are similar among expressed wild-type and mutant ectodomain peptides. Circular dichroism measurements reveal decreased thermal stability of the G541R mutant as compared to wild type. The G541R mutant also renders the peptide more susceptible to Lys-C protease cleavage. The 42-114 monoclonal antibody does not bind to the G541R mutant peptides, suggesting a structural difference from wild type. These altered physical properties result in productive viral infection of G541R bearing virus with decreased syncytia.
authors.affiliation: UMDNJ-Robert Wood Johnson Medical School, Department of Biochemistry, 675 Hoes Lane Rm. 636, Piscataway, NJ 08854, USA. schneiwm@umdnj.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Schneider
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zheng
authors.forename: Marie L
authors.initials: ML
authors.lastname: Coté
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Roth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002942:Circular Dichroism; D004926:Escherichia coli / Q000235:genetics; D006358:Hot Temperature; D009052:Leukemia Virus, Murine / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D014759:Viral Envelope Proteins