Peptide Fragments of Odin‐Sam1: Conformational Analysis and Interaction Studies with EphA2‐Sam |
| |
| Authors: | Dr. Flavia A. Mercurio Concetta Di Natale Dr. Luciano Pirone Dr. Pasqualina L. Scognamiglio Dr. Daniela Marasco Dr. Emilia M. Pedone Dr. Michele Saviano Dr. Marilisa Leone |
| |
| Affiliation: | 1. Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone 16, 80134, Naples (Italy);2. Department of Pharmacy, University of Naples “Federico II”, Via Mezzocannone 16, 80134, Naples (Italy);3. Current address: Center for Advanced Biomaterials for Health Care@CRIB, Via Largo Barsanti e Matteucci 53, 80125, Naples (Italy);4. Circmsb (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici), Via C. Ulpiani 27, 70126 Bari (Italy);5. Cirpeb (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), Via Mezzocannone 16, 80134, Naples (Italy);6. Institute of Crystallography, National Research Council, Via Giovanni Amendola 122/O, 70126, Bari (Italy) |
| |
| 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. |
| |
| Keywords: | Epha2 NMR spectroscopy peptides Sam domain surface plasmon resonance |
|
|
