title: Structural investigation on the intrinsically disordered N-terminal region of HPV16 E7 protein.
abstract: Human papillomavirus (HPV) is the major cause of cervical cancer, a deadly threat to millions of females. The early oncogene product (E7) of the high-risk HPV16 is the primary agent associated with HPV-related cervical cancers. In order to understand how E7 contributes to the transforming activity, we investigated the structural features of the flexible N-terminal region (46 residues) of E7 by carrying out N-15 heteronuclear NMR experiments and replica exchange molecular dynamics simulations. Several NMR parameters as well as simulation ensemble structures indicate that this intrinsically disordered region of E7 contains two transient (10-20% populated) helical pre-structured motifs that overlap with important target binding moieties such as an E2F-mimic motif and a pRb-binding LXCXE segment. Presence of such target-binding motifs in HPV16 E7 provides a reasonable explanation for its promiscuous target-binding behavior associated with its transforming activity. [BMB Reports 2016; 49(8): 431-436].
authors.affiliation: Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.
authors.forename: Chewook
authors.initials: C
authors.lastname: Lee
authors.affiliation: Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.
authors.forename: Do-Hyoung
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.
authors.forename: Si-Hyung
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141; Department of Bioinformatics, University of Science and Technology, Daejeon 34113, Korea.
authors.forename: Jiulong
authors.initials: J
authors.lastname: Su
authors.affiliation: Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141; Department of Bioinformatics, University of Science and Technology, Daejeon 34113, Korea.
authors.forename: Kyou-Hoon
authors.initials: KH
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008958:Models, Molecular; D050725:Papillomavirus E7 Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D064267:Intrinsically Disordered Proteins; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16