A membranotropic region in the C-terminal domain of Hepatitis C virus protein NS4B: Interaction with membranes |
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Authors: | Jaime Guillé n |
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Affiliation: | Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, E-03202, Elche-Alicante, Spain |
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Abstract: | We have identified a membrane-active region in the HCV NS4B protein by studying membrane rupture induced by a NS4B-derived peptide library on model membranes. This segment corresponds to one of two previously predicted amphipathic helix and define it as a new membrane association domain. We report the binding and interaction with model membranes of a peptide patterned after this segment, peptide NS4BH2, and show that NS4BH2 strongly partitions into phospholipid membranes, interacts with them, and is located in a shallow position in the membrane. Furthermore, changes in the primary sequence cause the disruption of the hydrophobicity along the structure and prevent the resulting peptide from interacting with the membrane. Our results suggest that the region where the NS4BH2 is located might have an essential role in the membrane replication and/or assembly of the viral particle through the modulation of the replication complex. Our findings therefore identify an important region in the HCV NS4B protein which might be implicated in the HCV life cycle and possibly in the formation of the membranous web. |
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Keywords: | BPI, Bovine brain smallcaps" >l-α-phosphadidylinositol BPS, Bovine brain smallcaps" >l-α-phosphatidylserine CF, 5-Carboxyfluorescein Chol, Cholesterol di-8-ANEPPS, 4-(2-(6-(Dioctylamino)-2-naphthalenyl)-(ethenyl)-1-(3-sulfopropyl)-pyridinium inner salt DMPC, 1,2-Dimyristoyl-sn-glycero-phosphatidylcholine DMPG, 1,2-Dimyristoyl-sn-glycero-phosphatidylglycerol DMPS, 1,2-Dimyristoyl-sn-glycero-3-phosphatidylserine DPH, 1,6-Diphenyl-1,3,5-hexatriene DSC, Differential Scanning Calorimetry EPA, Egg smallcaps" >l-α-phosphatidic acid EPC, Egg smallcaps" >l-α-phosphatidylcholine EPG, Egg smallcaps" >l-α-phosphatidylglycerol ER, Endoplasmic reticulum FD10/20/70, Fluorescein isothiocyanate dextran with an average molecular weight of 10,000/20,000/70,000 HCV, Hepatitis C virus LUV, Large unilamellar vesicles MLV, Multilamellar vesicles NS, Non-structural protein SC1/2, Scrambled peptide 1/2 SM, Egg sphingomyelin SUV, Small unilamellar vesicles TFE, Trifluoroethanol Tm, Temperature of the gel-to-liquid crystalline phase transition TM, Transmembrane domain TMA-DPH, 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene TPE, Egg trans-esterified smallcaps" >l-α-phosphatidylethanolamine |
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