title: Membrane protein lateral interactions control Semliki Forest virus budding.
abstract: Semliki Forest virus, SFV, directs the synthesis of two membrane proteins, p62 and E1, which form a p62E1 heterodimer in the endoplasmic reticulum. After being transported to the plasma membrane (PM), they are incorporated into the virus membrane during the process of virus budding. Electronmicroscopic analyses of the envelope in matured virus show that the heterodimers are clustered into trimeric structures (spikes) which further form a regular surface lattice with T = 4. In this work we have used a genetic approach to study the importance of the trimerization event for virus budding. We have coexpressed a budding competent form of the virus heterodimer with another one which cannot be used for particle formation because of a defect in nucleocapsid (NC) binding. We show that the NC binding-deficient heterodimer is able to inhibit the budding of the competent one in a concentration-dependent manner and that the NC binding-competent heterodimers can rescue the incompetent ones into virus particles. This suggests that the heterodimers are complexed together, probably into the trimeric structures (spikes), at the PM to expose a multivalent binding site for the NC and thereby drive efficient virus budding.
authors.affiliation: Department of Molecular Biology, Karolinska Institute, Huddinge, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ekström
authors.forename: P
authors.initials: P
authors.lastname: Liljeström
authors.forename: H
authors.initials: H
authors.lastname: Garoff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016384:Consensus Sequence; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007668:Kidney; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D012672:Semliki forest virus / Q000254:growth & development* / Q000378:metabolism; D014162:Transfection; D014759:Viral Envelope Proteins / Q000096:biosynthesis*
chemical_list: D008565:Membrane Proteins; D014759:Viral Envelope Proteins