Heterotypic Sam-Sam Association Between Odin-Sam1 And Arap3-Sam: Binding Affinity And Structural Insights(505 views) Mercurio FA, Marasco D, Pirone L, Scognamiglio PL, Pedone E, Pellecchia M, Leone M
Chembiochem (ISSN: 1439-4227, 1439-9422, 1439-7633), 2013 Jan 2; 14(1): 100-106.
Keywords: Isothermal Titration Calorimetry, Nmr Spectroscopy, Protein-Protein Interactions, Sam Domains, Surface Plasmon Resonance, Arap3 Protein, Odin Protein, Phosphatidylinositol 3 Kinase, Sterile Alpha Motif 1 Protein, Sterile Alpha Motif Protein, Unclassified Drug, Amino Acid Sequence, Article, Binding Affinity, Molecular Docking, Molecular Model, Nuclear Magnetic Resonance Spectroscopy, Priority Journal, Protein Binding, Protein Domain, Protein Expression, Protein Protein Interaction, Protein Structure, Adaptor Proteins, Signal Transducing, Gtpase-Activating Proteins, Humans, Molecular Docking Simulation, Tertiary, Signal Transducing Chemistry Metabolism, Gtpase-Activating Proteins Chemistry Metabolism,
Affiliations: *** IBB - CNR ***
Department of Biological Sciences, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy
Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone 16, 80134 Naples, Italy
Institute of Crystallography, National Research Council, Via Giovanni Amendola 122/O, 70126 Bari, Italy
Infectious Diseases and Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, United States
References: Not available.
Heterotypic Sam-Sam Association Between Odin-Sam1 And Arap3-Sam: Binding Affinity And Structural Insights
Arap3 is a phosphatidylinositol 3 kinase effector protein that plays a role as GTPase activator (GAP) for Arf6 and RhoA. Arap3 contains a sterile alpha motif (Sam) domain that has high sequence homology with the Sam domain of the EphA2-receptor (EphA2-Sam). Both Arap3-Sam and EphA2-Sam are able to associate with the Sam domain of the lipid phosphatase Ship2 (Ship2-Sam). Recently, we reported a novel interaction between the first Sam domain of Odin (Odin-Sam1), a protein belonging to the ANKS (ANKyrin repeat and Sam domain containing) family, and EphA2-Sam. In our latest work, we applied NMR spectroscopy, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) to characterize the association between Arap3-Sam and Odin-Sam1. We show that these two Sam domains interact with low micromolar affinity. Moreover, by means of molecular docking techniques, supported by NMR data, we demonstrate that Odin-Sam1 and Arap3-Sam might bind with a topology that is common to several Sam-Sam complexes. The revealed structural details form the basis for the design of potential peptide antagonists that could be used as chemical tools to investigate functional aspects related to heterotypic Arap3-Sam associations. 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Heterotypic Sam-Sam Association Between Odin-Sam1 And Arap3-Sam: Binding Affinity And Structural Insights