title: Weak Selectivity Predicted for Modeled Bundles of Viral Channel-Forming Protein E5 of Human Papillomavirus-16.
abstract: Protein E5 is a polytopic 83 amino acid membrane protein with three transmembrane domains (TMDs), encoded by high-risk human papillomavirus-16 (HPV-16). HPV-16 is found to be the causative agent for cervical cancer. Protein E5, among other proteins (e.g., E6, E7), is expressed at an "early" (E) stage when the cell turns malignant. It has been experimentally found that E5 forms hexameric assemblies, which show the characteristics of the class of so-called channel-forming proteins by rendering lipid membranes permeable to ions and small molecules. Protein E5 is used to achieve structural models of the protein in assembled bundles using a force field-based docking approach. Extended molecular dynamics simulations of selected bundles in fully hydrated lipid bilayers suggest the second TMD to be pore-lining, allowing for water columns to exist within the lumen of the pore. Full correlation analysis indicates asymmetric dynamics within the monomers of the bundle. Potential of mean force calculations of a snapshot structure of the putative open pore of the protein bundle propose low selectivity.
authors.affiliation: Institute of Biophotonics and Biophotonics & Molecular Imaging Research Center (BMIRC), School of Biomedical Science and Engineering, National Yang-Ming University , Taipei 112, Taiwan.
authors.forename: Dhani Ram
authors.initials: DR
authors.lastname: Mahato
authors.affiliation: Institute of Biophotonics and Biophotonics & Molecular Imaging Research Center (BMIRC), School of Biomedical Science and Engineering, National Yang-Ming University , Taipei 112, Taiwan.
authors.forename: Wolfgang B
authors.identifier: 0000-0001-7753-1828
authors.initials: WB
authors.lastname: Fischer
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D052162:Human papillomavirus 16 / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009856:Oncogene Proteins, Viral / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*; D000086082:Viroporin Proteins
chemical_list: D008051:Lipid Bilayers; D009856:Oncogene Proteins, Viral; D010713:Phosphatidylcholines; D014867:Water; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins; C028694:1-palmitoyl-2-oleoylphosphatidylcholine