Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration

Amy Rice, Sourav Haldar, Eric Wang, Paul S. Blank, Sergey A. Akimov, Timur R. Galimzyanov, Richard W. Pastor and Joshua Zimmerberg ()
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Amy Rice: National Institutes of Health
Sourav Haldar: National Institutes of Health
Eric Wang: National Institutes of Health
Paul S. Blank: National Institutes of Health
Sergey A. Akimov: Russian Academy of Sciences
Timur R. Galimzyanov: Russian Academy of Sciences
Richard W. Pastor: National Institutes of Health
Joshua Zimmerberg: National Institutes of Health

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract To infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out from the viral surface to embed into the target cellular membrane. Here we report that synthesized influenza virus FPs are membrane active, generating pores in giant unilamellar vesicles (GUV), and thus potentially explain both influenza virus’ hemolytic activity and the liposome poration seen in cryo-electron tomography. Experimentally, FPs are heterogeneously distributed on the GUV at the time of poration. Consistent with this heterogeneous distribution, molecular dynamics (MD) simulations of asymmetric bilayers with different numbers of FPs in one leaflet show FP aggregation. At the center of FP aggregates, a profound change in the membrane structure results in thinning, higher water permeability, and curvature. Ultimately, a hybrid bilayer nanodomain forms with one lipidic leaflet and one peptidic leaflet. Membrane elastic theory predicts a reduced barrier to water pore formation when even a dimer of FPs thins the membrane as above, and the FPs of that dimer tilt, to continue the leaflet bending initiated by the hydrophobic mismatch between the FP dimer and the surrounding lipid.

Date: 2022
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DOI: 10.1038/s41467-022-34576-z

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