Fatty acids on the A/Japan/305/57 influenza virus hemagglutinin have a role in membrane fusion.
The covalent attachment of fatty acid moieties to proteins is a widespread post-translational modification of viral and cell proteins yet the functional consequences of acylation are not well understood. We have determined that the A/Japan/305/57 influenza virus hemagglutinin (HA) contains three potential acylation sites at cysteine residues 211, 218 and 221 in the cytoplasmic domain of the molecule. Site-directed mutagenesis of one or more of these sites has no effect on biosynthesis, transport or receptor binding activity of the molecule; however, modification of any single site is sufficient to abolish completely or inhibit severely membrane fusion activity, a function essential for virus infectivity. We present a molecular model of the transmembrane and cytoplasmic domains of the HA to illustrate the potential orientation of these fatty acids and to provide a conceptual framework for further experimentation.
Naeve
C W
CW
Department of Virology and Molecular Biology, St Jude Children's Research Hospital, Memphis, TN 38101.
Williams
D
D
D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003196:Computer Graphics; D005227:Fatty Acids / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005814:Genes, Viral; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000502:physiology*; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D008051:Lipid Bilayers; D008561:Membrane Fusion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational
D005227:Fatty Acids; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008051:Lipid Bilayers; D010169:Palmitic Acids; D019308:Palmitic Acid