Structural Investigations on the Nodal-Cripto Binding: A Theoretical and Experimental Approach(562 views) Calvanese L, Marasco D, Doti N, Saporito A, D'Auria G, Paolillo L, Ruvo M, Falcigno L
Keywords: Binding, Homology Modeling, K D, Peptide, Tgf-β, Binding Affinities, Embryonic Development, Experimental Approaches, K D< Sub>, Molecular Models, Morphogen, Nodal Region, Potential Binding, Receptor-Like Kinase, Structural Information, Structural Investigation, Surface Plasmon Resonance Binding Assays, Synthetic Peptide, Transforming Growth Factors, Tumor Progressions, Binding Energy, Activin Receptor Like Kinase 1, Nodal Signaling Protein, Protein Cripto, Unclassified Drug, Amino Acid Sequence, Article, Experimental Study, Human, Molecular Docking, Nonhuman, Nucleotide Sequence, Protein Binding, Protein Protein Interaction, Protein Structure, Sequence Homology, Theoretical Study, Type I, Animals, Binding Sites, Epidermal Growth Factor, Membrane Glycoproteins, Molecular Sequence Data, Molecular Structure, Multiprotein Complexes, Neoplasm Proteins, Nodal Protein, Nuclear Magnetic Resonance, Biomolecular, Recombinant Proteins, Type I Chemistry Metabolism, Epidermal Growth Factor Chemistry Genetics Metabolism, Gpi-Linked Proteins, In Vitro Techniques, Intercellular Signaling Peptides And Proteins, Membrane Glycoproteins Chemistry Genetics Metabolism, Multiprotein Complexes Chemistry, Neoplasm Proteins Chemistry Genetics Metabolism, Nodal Protein Chemistry Genetics Metabolism, Recombinant Proteins Chemistry Genetics Metabolism,
Affiliations: *** IBB - CNR ***
Department of Chemistry P. Corradini, University of Naples Federico II, Via Cintia 45, 80126 Naples, Italy
Department of Biological Sciences, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy
Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone, 16, 80134 Naples, Italy
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Structural Investigations on the Nodal-Cripto Binding: A Theoretical and Experimental Approach
Nodal, a member of the transforming growth factor-beta superfamily, is a potent embryonic morphogen also implicated in tumor progression. Up to date structural information on the interaction of Nodal with its molecular partners are unknown. To deepen our understanding about mechanisms underlying both embryonic development and Nodal/Cripto-dependent tumor progression, we present here a molecular model of activin receptor-like kinase 4/Cripto/Nodal complex built by homology modeling as well as docking tests aimed at identifying potential binding epitopes. Starting from this model, we have predicted a large interaction surface on Nodal, which encompasses residues 43-69 and includes the prehelix loop and the H3 helix. This hypothesis has been subsequently assessed by surface plasmon resonance binding assays between the full-length Cripto and synthetic peptides reproducing the selected Nodal regions. In addition, the binding affinity between the full-length Nodal and Cripto proteins has been evaluated for the first time. (C) 2010 Wiley Periodicals, Inc. Biopolymers 93: 1011-1021, 2010.
Structural Investigations on the Nodal-Cripto Binding: A Theoretical and Experimental Approach
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Structural Investigations on the Nodal-Cripto Binding: A Theoretical and Experimental Approach