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

9 Citations (Scopus)

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

Fingerprint

Cholesterol
Peptides
Membranes
Virus Assembly
Unilamellar Liposomes
Hepacivirus
Endoplasmic Reticulum
Lipids
Population
Proteins

ASJC Scopus subject areas

  • Biophysics

Cite this

Hanson, J. M., Gettel, D. L., Tabaei, S. R., Jackman, J., Kim, M. C., Sasaki, D. Y., ... 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

Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide. / Hanson, Joshua M.; Gettel, Douglas L.; Tabaei, Seyed R.; Jackman, Joshua; Kim, Min Chul; Sasaki, Darryl Y.; Groves, Jay T.; Liedberg, Bo; Cho, Nam Joon; Parikh, Atul N.

In: Biophysical Journal, Vol. 110, No. 1, 05.01.2016, p. 176-187.

Research output: Contribution to journalArticle

Hanson, JM, Gettel, DL, Tabaei, SR, Jackman, J, Kim, MC, Sasaki, DY, Groves, JT, Liedberg, B, Cho, NJ & Parikh, AN 2016, 'Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide', Biophysical Journal, vol. 110, no. 1, pp. 176-187. https://doi.org/10.1016/j.bpj.2015.11.032
Hanson, Joshua M. ; Gettel, Douglas L. ; Tabaei, Seyed R. ; Jackman, Joshua ; Kim, Min Chul ; Sasaki, Darryl Y. ; Groves, Jay T. ; Liedberg, Bo ; Cho, Nam Joon ; Parikh, Atul N. / Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide. In: Biophysical Journal. 2016 ; Vol. 110, No. 1. pp. 176-187.
@article{321328f154e84f6cb5be5826b69bfb50,
title = "Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide",
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.",
author = "Hanson, {Joshua M.} and Gettel, {Douglas L.} and Tabaei, {Seyed R.} and Joshua Jackman and Kim, {Min Chul} and Sasaki, {Darryl Y.} and Groves, {Jay T.} and Bo Liedberg and Cho, {Nam Joon} and Parikh, {Atul N.}",
year = "2016",
month = "1",
day = "5",
doi = "10.1016/j.bpj.2015.11.032",
language = "English (US)",
volume = "110",
pages = "176--187",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "1",

}

TY - JOUR

T1 - Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide

AU - Hanson, Joshua M.

AU - Gettel, Douglas L.

AU - Tabaei, Seyed R.

AU - Jackman, Joshua

AU - Kim, Min Chul

AU - Sasaki, Darryl Y.

AU - Groves, Jay T.

AU - Liedberg, Bo

AU - Cho, Nam Joon

AU - Parikh, Atul N.

PY - 2016/1/5

Y1 - 2016/1/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84953403021&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953403021&partnerID=8YFLogxK

U2 - 10.1016/j.bpj.2015.11.032

DO - 10.1016/j.bpj.2015.11.032

M3 - Article

VL - 110

SP - 176

EP - 187

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 1

ER -