Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide

Joshua M. Hanson, Douglas L. Gettel, Seyed R. Tabaei, Joshua Jackman, Min Chul Kim, Darryl Y. Sasaki, Jay T. Groves, Bo Liedberg, Nam Joon Cho, Atul N. Parikh

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The α-helical (AH) domain of the hepatitis C virus nonstructural protein NS5A, anchored at the cytoplasmic leaflet of the endoplasmic reticulum, plays a role in viral replication. However, the peptides derived from this domain also exhibit remarkably broad-spectrum virocidal activity, raising questions about their modes of membrane association. Here, using giant lipid vesicles, we show that the AH peptide discriminates between membrane compositions. In cholesterol-containing membranes, peptide binding induces microdomain formation. By contrast, cholesterol-depleted membranes undergo global softening at elevated peptide concentrations. Furthermore, in mixed populations, the presence of ∼100 nm vesicles of viral dimensions suppresses these peptide-induced perturbations in giant unilamellar vesicles, suggesting size-dependent membrane association. These synergistic composition- and size-dependent interactions explain, in part, how the AH domain might on the one hand segregate molecules needed for viral assembly and on the other hand furnish peptides that exhibit broad-spectrum virocidal activity.

Original languageEnglish (US)
Pages (from-to)176-187
Number of pages12
JournalBiophysical Journal
Volume110
Issue number1
DOIs
StatePublished - Jan 5 2016

ASJC Scopus subject areas

  • Biophysics

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    Hanson, J. M., Gettel, D. L., Tabaei, S. R., Jackman, J., Kim, M. C., Sasaki, D. Y., Groves, J. T., Liedberg, B., Cho, N. J., & Parikh, A. N. (2016). Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide. Biophysical Journal, 110(1), 176-187. https://doi.org/10.1016/j.bpj.2015.11.032