title: Turning of the receptor-binding domains opens up the murine leukaemia virus Env for membrane fusion.
abstract: The activity of the membrane fusion protein Env of Moloney mouse leukaemia virus is controlled by isomerization of the disulphide that couples its transmembrane (TM) and surface (SU) subunits. We have arrested Env activation at a stage prior to isomerization by alkylating the active thiol in SU and compared the structure of isomerization-arrested Env with that of native Env. Env trimers of respective form were isolated from solubilized particles by sedimentation and their structures were reconstructed from electron microscopic images of both vitrified and negatively stained samples. We found that the protomeric unit of both trimers formed three protrusions, a top, middle and a lower one. The atomic structure of the receptor-binding domain of SU fitted into the upper protrusion. This was formed similar to a bent finger. Significantly, in native Env the tips of the fingers were directed against each other enclosing a cavity below, whereas they had turned outward in isomerization-arrested Env transforming the cavity into an open well. This might subsequently guide the fusion peptides in extended TM subunits into the target membrane.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.
authors.forename: Shang-Rung
authors.initials: SR
authors.lastname: Wu
authors.forename: Mathilda
authors.initials: M
authors.lastname: Sjöberg
authors.forename: Michael
authors.initials: M
authors.lastname: Wallin
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lindqvist
authors.forename: Maria
authors.initials: M
authors.lastname: Ekström
authors.forename: Hans
authors.initials: H
authors.lastname: Hebert
authors.forename: Philip J B
authors.initials: PJ
authors.lastname: Koeck
authors.forename: Henrik
authors.initials: H
authors.lastname: Garoff
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D020285:Cryoelectron Microscopy / Q000379:methods; D015686:Gene Products, env / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D015752:Genes, env; D007091:Image Processing, Computer-Assisted; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D014760:Viral Fusion Proteins / Q000378:metabolism*
chemical_list: D015686:Gene Products, env; D014760:Viral Fusion Proteins
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