title: The interaction of synthetic analogs of the N-terminal fusion sequence of influenza virus with a lipid monolayer. Comparison of fusion-active and fusion-defective analogs.
abstract: The amino terminus of subunit-2 of influenza virus hemagglutinin (NHA2) plays a crucial role in the induction of fusion between viral and endosomal membranes leading to the infection of a cell. Three synthetic analogs with an amino acid sequence corresponding to NHA2 of variant hemagglutinins were studied in a monolayer set up. Comparison of the interaction of a fusion-active and two fusion-defective analogs with a lipid monolayer revealed a greater surface activity of the fusion-active analog. Pronounced differences were found if the pure peptides were spread at the air/water interface; the fusion-active analog showed a higher collapse pressure and a greater limiting molecular area. Circular dichroism measurements on collected lipid monolayers indicated a high content of alpha-helical structure for the fusion-active and one of the fusion-defective analogs. A simple relation between alpha-helical content and fusogenicity does not seem to exist. Instead, the extent of penetration, a defined tertiary structure or orientation of the alpha-helical peptide may be essential for its membrane perturbing activity.
authors.affiliation: Institute of Molecular Biology and Medical Biotechnology, University of Utrecht, The Netherlands.
authors.forename: K N
authors.initials: KN
authors.lastname: Burger
authors.forename: S A
authors.initials: SA
authors.lastname: Wharton
authors.forename: R A
authors.initials: RA
authors.lastname: Demel
authors.forename: A J
authors.initials: AJ
authors.lastname: Verkleij
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000502:physiology*; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000502:physiology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D011312:Pressure; D011487:Protein Conformation; D013499:Surface Properties
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008563:Membrane Lipids; D010446:Peptide Fragments