title: Composition and functions of the influenza fusion peptide.
abstract: Fusion of the influenza virus envelope with the endosomal membrane of host cells is mediated by the hemagglutinin glycoprotein (HA). The most conserved region of HA is at the N-terminus of the HA2 subunit, a relatively hydrophobic sequence of amino acids referred to as the fusion peptide. This domain is critical both for setting the trigger for fusion and for destabilizing target membranes during the fusion process. The "trigger" is set by cleavage of the HA precursor polypeptide, when the newly-generated HA2 N-terminal fusion peptide positions itself into the trimer interior and makes contacts with ionizable residues to generate a fusion competent neutral pH structure. This essentially "primes" the HA such that subsequent acidification of the endosomal environment can induce the irreversible conformational changes that result in membrane fusion. A key component of these acid-induced structural rearrangements involves the extrusion of the fusion peptide from its buried position and its relocation to interact with the target membrane. The role of the fusion peptide for both priming the neutral pH structure and interacting with cellular membranes during the fusion process is discussed.
authors: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
authors: Karen J
authors: KJ
authors: Cross
authors: William A
authors: WA
authors: Langley
authors: Rupert J
authors: RJ
authors: Russell
authors: John J
authors: JJ
authors: Skehel
authors: David A
authors: DA
authors: Steinhauer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000378:metabolism*; D011487:Protein Conformation; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014760:Viral Fusion Proteins