title: The membrane spanning domains of protein NS4B from hepatitis C virus.
abstract: Determination of the membrane spanning domains of highly hydrophobic proteins from its primary structure, i.e., sequence, is cumbersome. However, transmembrane topology is better correlated with protein secondary structure than with the primary one. In this work we have determined the number and location of the transmembrane domains of the highly hydrophobic hepatitis C virus NS4B protein by studying the water-to-bilayer and water-to-interface transfer free energies of thirty-one different hepatitis C virus strains assuming that NS4B forms an α-helical wheel. Additionally, we have studied the effect of a peptide library encompassing the full length of the NS4B protein hepatitis C virus strain 1a_H77 on the phase transitions of DEPE through the use of differential scanning calorimetry. Our findings show that NS4B protein has five transmembrane domains and, as previously suggested, three interfacial segments. One of these segments, segment AH2, could behave similarly to viral pre-transmembrane segments, which would partition into and interact with the membrane and be responsible for the fluctuation of the protein between different topologies and therefore possible locations.
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, E-03202 Elche-Alicante, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Palomares-Jerez
authors.forename: Henrique
authors.initials: H
authors.lastname: Nemesio
authors.forename: José
authors.initials: J
authors.lastname: Villalaín
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism / Q000821:virology; D016174:Hepacivirus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C080107:NS4B protein, flavivirus; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins