title: Protein-protein interactions: modeling the hepatitis C virus ion channel p7.
abstract: The p7 protein is a small ion-channel-forming membrane polypeptide encoded by the hepatitis C virus which consists of two transmembrane alpha-helices, TM1 and TM2, and can be blocked by long-alkyl-chain iminosugar derivatives. The length of TM1 and TM2 was estimated by employing different secondary structure prediction algorithms and is proposed to span from Ala-10 to Leu-32 for TM1 and from Trp-36 to Pro-58 for TM2. A configurational search protocol based on simulated annealing combined with short restrained molecular dynamics simulations is used in addition to protein-protein docking to investigate the packing of TM1/TM2. Full p7 oligomeric bundles were generated, and in the most plausible models serines and threonines are facing the hydrophilic pore. In these models, His-17 would be a pore-facing residue, suggesting that p7 may be sensitive to pH in respect to its function.
authors.affiliation: Biomembrane Structure Unit, Department of Biochemistry, Oxford University, Oxford OX1 3QU, UK.
authors.forename: George
authors.initials: G
authors.lastname: Patargias
authors.forename: Nicole
authors.initials: N
authors.lastname: Zitzmann
authors.forename: Raymond
authors.initials: R
authors.lastname: Dwek
authors.forename: Wolfgang B
authors.initials: WB
authors.lastname: Fischer
mesh_terms: D000547:Amantadine / Q000737:chemistry; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry; D016174:Hepacivirus; D007473:Ion Channels / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
chemical_list: D000547:Amantadine; D000998:Antiviral Agents; D007473:Ion Channels; D008565:Membrane Proteins; D010455:Peptides; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins