title: Peptide Fragments of Odin-Sam1: Conformational Analysis and Interaction Studies with EphA2-Sam.
abstract: Odin is a protein belonging to the ANKS family, and has two tandem Sam domains. The first, Odin-Sam1, binds to the Sam domain of the EphA2 receptor (EphA2-Sam); this interaction could be crucial for the regulation of receptor endocytosis and might have an impact on cancer. Odin-Sam1 associates with EphA2-Sam by adopting a "mid-loop/end-helix" model. In this study three peptide sequences, encompassing the mid-loop interacting portion of Odin-Sam1 and its C-terminal α5 helix, were designed. Their conformational properties were analyzed by CD and NMR. In addition, their abilities to interact with EphA2-Sam were investigated by SPR studies. The peptides adopt a predominantly disordered state in aqueous buffer, but a higher helical content is evident in the presence of the cosolvent trifluoroethanol. Dissociation constants towards EphA2-Sam were in the high micromolar range. The structural findings suggest further routes for the design of potential anti-cancer therapeutics as inhibitors of EphA2-Sam heterotypic interactions.
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone 16, 80134, Naples (Italy).
authors.forename: Flavia A
authors.initials: FA
authors.lastname: Mercurio
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples (Italy).|Current address: Center for Advanced Biomaterials for Health Care@CRIB, Via Largo Barsanti e Matteucci 53, 80125, Naples (Italy).
authors.forename: Concetta
authors.initials: C
authors.lastname: Di Natale
authors.affiliation: Circmsb (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici), Via C. Ulpiani 27, 70126 Bari (Italy).
authors.forename: Luciano
authors.initials: L
authors.lastname: Pirone
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples (Italy).|Cirpeb (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), Via Mezzocannone 16, 80134, Naples (Italy).|Current address: Center for Advanced Biomaterials for Health Care@CRIB, Via Largo Barsanti e Matteucci 53, 80125, Naples (Italy).
authors.forename: Pasqualina L
authors.initials: PL
authors.lastname: Scognamiglio
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone 16, 80134, Naples (Italy).|Department of Pharmacy, University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples (Italy).|Cirpeb (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), Via Mezzocannone 16, 80134, Naples (Italy).
authors.forename: Daniela
authors.initials: D
authors.lastname: Marasco
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone 16, 80134, Naples (Italy).|Cirpeb (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), Via Mezzocannone 16, 80134, Naples (Italy).
authors.forename: Emilia M
authors.initials: EM
authors.lastname: Pedone
authors.affiliation: Cirpeb (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), Via Mezzocannone 16, 80134, Naples (Italy).|Institute of Crystallography, National Research Council, Via Giovanni Amendola 122/O, 70126, Bari (Italy).
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone 16, 80134, Naples (Italy). marilisa.leone@cnr.it.|Cirpeb (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), Via Mezzocannone 16, 80134, Naples (Italy). marilisa.leone@cnr.it.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Leone
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D036104:Receptor, EphA2 / Q000737:chemistry* / Q000378:metabolism*; D014270:Trifluoroethanol / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: C557872:ANKS1A protein, human; D048868:Adaptor Proteins, Signal Transducing; D010446:Peptide Fragments; D014867:Water; D014270:Trifluoroethanol; D036104:Receptor, EphA2
keywords: Epha2; NMR spectroscopy; Sam domain; peptides; surface plasmon resonance