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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Hanson JM,Gettel DL,Tabaei SR,Jackman J,Kim MC,Sasaki DY,Groves JT,Liedberg B,Cho NJ,Parikh AN

doi

10.1016/j.bpj.2015.11.032

subject

Has Abstract

pub_date

2016-01-05 00:00:00

pages

176-87

issue

1

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(15)01215-1

journal_volume

110

pub_type

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