title: An aromatic side chain is required at residue 8 of SU for fusion of ecotropic murine leukemia virus.
abstract: The surface glycoprotein (SU) of most gammaretroviruses contains a conserved histidine at its amino terminus. In ecotropic murine leukemia virus SU, replacement of histidine 8 with arginine (H8R) or deletion of H8 (H8del) abolishes infection and cell-cell fusion but has no effect on binding to the cellular receptor. We report here that an aromatic ring side chain is essential to the function of residue 8. The size of the aromatic ring appears to be important, as does its ability to form a hydrogen bond. In addition, infection by all of the nonaromatic amino acid substitutions could be partially rescued by the addition of two suppressor mutations (glutamine 227 to arginine [Q227R] and aspartate 243 to tyrosine [D243Y]) or by exposure to chlorpromazine, an agent that induces fusion pores in hemifusion intermediates to complete fusion, suggesting that, like the previously described H8R mutant, the mutants reported here also arrest membrane fusion at the hemifusion state. We propose that H8 is a key switch-point residue in the conformation changes that lead to membrane fusion and present a possible mechanism for how its substitution arrests fusion at the hemifusion state.
authors.affiliation: Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Qian
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Albritton
mesh_terms: D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000378:metabolism / Q000472:pathogenicity*; D008561:Membrane Fusion; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D011487:Protein Conformation; D011991:Receptors, Virus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D002746:Chlorpromazine