Characterization of a region of the measles virus hemagglutinin sufficient for its dimerization.
Attachment of measles virus (MV) to its cellular receptor is mediated by the viral envelope glycoprotein hemagglutinin (H). H exists at the viral surface as a disulfide-linked dimer which may associate into a tetramer. We aimed to define regions of H essential for its homo-oligomerization. To delineate these more precisely, we have generated a series of H ectodomain truncation mutants and studied their abilities to form both homotypic complexes and heterotypic complexes with full-length H. We define a "minimal unit" which is sufficient for MV H dimerization as that encompassing residues 1 to 151. This unit forms both homodimers and heterodimers with full-length H protein, although neither is transported to the cell surface even in the presence of other MV proteins. We show that cysteine residues at positions 139 and 154 are both critical in mediating covalent dimerization, not only of the truncated H mutants but also of full-length MV H protein. Even those cysteine mutants unable to form covalent intermolecular interactions are biologically active, mediating the formation of syncytia, albeit at a reduced rate. We demonstrate that this impaired capacity to mediate cell-to-cell fusion is based mainly on a reduced transport rate of the mutant molecules to the cell surface, indicating a role for covalent intermolecular interactions in efficient transport of MV H dimers to the cell surface.
Plemper
R K
RK
Molecular Medicine Program, Mayo Foundation, Rochester, Minnesota 55905, USA. plemper.richard@mayo.edu
Hammond
A L
AL
Cattaneo
R
R
D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D015726:Giant Cells / Q000821:virology; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008459:Measles virus / Q000737:chemistry* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D014709:Vero Cells
D006389:Hemagglutinins, Viral; C032397:hemagglutinin protein G, measles virus; D003545:Cysteine