Interaction of the influenza hemagglutinin fusion peptide with lipid bilayers: area expansion and permeation.
Fusion is a crucial event in the infection of animal cells by enveloped viruses (e.g., HIV or influenza). Viral fusion is mediated by glycoproteins, spanning the viral envelope, which attach to a membrane surface and induce fusion of the viral envelope to the cellular membrane. Influenza fusion protein (hemagglutinin) contains an amino-terminal segment critical to fusion, referred to as the fusion peptide. We show here that the native fusion peptide (wt-20) of hemagglutinin destabilizes membranes formed of 99% 1 -stearoyl-2-oleoylphosphatidylcholine (SOPC). The first step in destabilization is rapid insertion of the peptide into the membrane, in which membrane area increases by as much as 11% in just seconds. We visualized and quantified the area expansion by using optical video microscopy combined with micropipette aspiration. This rapid membrane area expansion is followed by the formation of membrane defects in the size range of 0.5 nm, and results in membrane rupture. Both the rate of area increase and maximum area increase are significantly higher at a pH near 5.0 compared to pH 7.0. These results suggest that enhanced membrane insertion of wt-20 and accompanying area expansion at pH 5.0 are responsible for the relatively greater lytic activity at this pH. We show that a deletion of the N-terminal glycine of wt-20 results in a lack of area expansion or membrane perturbation at pH 5.0.
Longo
M L
ML
School of Chemical Engineering, Cornell University, Ithaca, New York 14853, USA.
Waring
A J
AJ
Hammer
D A
DA
D000595:Amino Acid Sequence; D001703:Biophysics / Q000295:instrumentation / Q000379:methods; D006678:HIV / Q000737:chemistry / Q000502:physiology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000737:chemistry / Q000502:physiology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D013329:Structure-Activity Relationship
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; C027891:1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine