title: Amino acid sequence requirements of the transmembrane and cytoplasmic domains of influenza virus hemagglutinin for viable membrane fusion.
abstract: The amino acid sequence requirements of the transmembrane (TM) domain and cytoplasmic tail (CT) of the hemagglutinin (HA) of influenza virus in membrane fusion have been investigated. Fusion properties of wild-type HA were compared with those of chimeras consisting of the ectodomain of HA and the TM domain and/or CT of polyimmunoglobulin receptor, a nonviral integral membrane protein. The presence of a CT was not required for fusion. But when a TM domain and CT were present, fusion activity was greater when they were derived from the same protein than derived from different proteins. In fact, the chimera with a TM domain of HA and truncated CT of polyimmunoglobulin receptor did not support full fusion, indicating that the two regions are not functionally independent. Despite the fact that there is wide latitude in the sequence of the TM domain that supports fusion, a point mutation of a semiconserved residue within the TM domain of HA inhibited fusion. The ability of a foreign TM domain to support fusion contradicts the hypothesis that a pore is composed solely of fusion proteins and supports the theory that the TM domain creates fusion pores after a stage of hemifusion has been achieved.
authors.affiliation: Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois 60612, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Melikyan
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: M G
authors.initials: MG
authors.lastname: Roth
authors.forename: F S
authors.initials: FS
authors.lastname: Cohen
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane; D003593:Cytoplasm; D004912:Erythrocytes / Q000378:metabolism / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008561:Membrane Fusion / Q000502:physiology*; D008969:Molecular Sequence Data; D017354:Point Mutation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011994:Recombinant Proteins