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

Autor:	Hanson JM; Biophysics Graduate Group, University of California, Davis, Davis, California., Gettel DL; Department of Chemical Engineering & Materials Science, University of California, Davis, Davis, California., Tabaei SR; Centre for Biomimetic Sensor Science, Nanyang Technological University, Singapore; School of Materials Science and Engineering, Nanyang Technological University, Singapore., Jackman J; Centre for Biomimetic Sensor Science, Nanyang Technological University, Singapore; School of Materials Science and Engineering, Nanyang Technological University, Singapore., Kim MC; Centre for Biomimetic Sensor Science, Nanyang Technological University, Singapore; School of Materials Science and Engineering, Nanyang Technological University, Singapore., Sasaki DY; Biotechnology and Bioengineering Department, Sandia National Laboratories, Livermore, California., Groves JT; Chemistry Department, University of California, Berkeley, California; Mechanobiology Institute, National University of Singapore, Singapore., Liedberg B; Centre for Biomimetic Sensor Science, Nanyang Technological University, Singapore; School of Materials Science and Engineering, Nanyang Technological University, Singapore., Cho NJ; Centre for Biomimetic Sensor Science, Nanyang Technological University, Singapore; School of Materials Science and Engineering, Nanyang Technological University, Singapore; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore., Parikh AN; Biophysics Graduate Group, University of California, Davis, Davis, California; Department of Chemical Engineering & Materials Science, University of California, Davis, Davis, California; Centre for Biomimetic Sensor Science, Nanyang Technological University, Singapore; School of Materials Science and Engineering, Nanyang Technological University, Singapore; Department of Biomedical Engineering, University of California, Davis, Davis, California. Electronic address: anparikh@ucdavis.edu.
Jazyk:	angličtina
Zdroj:	Biophysical journal [Biophys J] 2016 Jan 05; Vol. 110 (1), pp. 176-87.
DOI:	10.1016/j.bpj.2015.11.032
Abstrakt:	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. (Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu