title: Properties and structures of the influenza and HIV fusion peptides on lipid membranes: implications for a role in fusion.
abstract: The fusion peptides of HIV and influenza virus are crucial for viral entry into a host cell. We report the membrane-perturbing and structural properties of fusion peptides from the HA fusion protein of influenza virus and the gp41 fusion protein of HIV. Our goals were to determine: 1), how fusion peptides alter structure within the bilayers of fusogenic and nonfusogenic lipid vesicles and 2), how fusion peptide structure is related to the ability to promote fusion. Fluorescent probes revealed that neither peptide had a significant effect on bilayer packing at the water-membrane interface, but both increased acyl chain order in both fusogenic and nonfusogenic vesicles. Both also reduced free volume within the bilayer as indicated by partitioning of a lipophilic fluorophore into membranes. These membrane ordering effects were smaller for the gp41 peptide than for the HA peptide at low peptide/lipid ratio, suggesting that the two peptides assume different structures on membranes. The influenza peptide was predominantly helical, and the gp41 peptide was predominantly antiparallel beta-sheet when membrane bound, however, the depths of penetration of Trps of both peptides into neutral membranes were similar and independent of membrane composition. We previously demonstrated: 1), the abilities of both peptides to promote fusion but not initial intermediate formation during PEG-mediated fusion and 2), the ability of hexadecane to compete with this effect of the fusion peptides. Taken together, our current and past results suggest a hypothesis for a common mechanism by which these two viral fusion peptides promote fusion.
authors.affiliation: Department of Biochemistry and Program in Molecular/Cell Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260, USA.
authors.forename: Md Emdadul
authors.initials: ME
authors.lastname: Haque
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Koppaka
authors.forename: Paul H
authors.initials: PH
authors.lastname: Axelsen
authors.forename: Barry R
authors.initials: BR
authors.lastname: Lentz
mesh_terms: D000595:Amino Acid Sequence; D016880:Anisotropy; D002462:Cell Membrane / Q000378:metabolism; D002725:Chloroform / Q000737:chemistry; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D014364:Tryptophan / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D015700:HIV Envelope Protein gp41; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008051:Lipid Bilayers; D008055:Lipids; D010455:Peptides; D010713:Phosphatidylcholines; D011993:Recombinant Fusion Proteins; D014867:Water; D011092:Polyethylene Glycols; D002725:Chloroform; D014364:Tryptophan; C017251:1,2-oleoylphosphatidylcholine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine