Protein-protein interactions: a simple strategy to identify binding sites and peptide antagonists(558 views) Sandomenico A, Monti SM, Sabatella M, De Capua A, Tornatore L, Doti N, Viparelli F, Dathan NA, Pedone C, Ruvo M, Marasco D
Chem Biol Drug Des (ISSN: 1747-0285, 1747-0277), 2009 May; 73(5): 483-493.
Keywords: Competition Assays, Mass Spectrometry, Proteolysis, Synthetic Peptides, Growth Arrest And Dna Damage Inducible Protein 45, Immunoglobulin Enhancer Binding Protein, Peptide Antagonist, Peptide Antibody, Phospholipase, Phosphoprotein, Protein Bcl 10, Unclassified Drug, Article, Binding Site, Circular Dichroism, Diabetes Mellitus, Gene Overexpression, In Vitro Study, Liquid Chromatography, Nonhuman, Peptide Synthesis, Priority Journal, Protein Degradation, Protein Domain, Protein Folding, Protein Protein Interaction, Protein Secondary Structure, Protein Structure, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Antigens, Differentiation, Intracellular Signaling Peptides And Proteins, Molecular Sequence Data, Multiprotein Complexes, Nf-Kappa B, Protein Binding, Protein Interaction Mapping, Tertiary,
Affiliations: *** IBB - CNR ***
Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134, Napoli, Italy.
Centro di Ricerca Interdipartimentale sui Biomateriali, Università di Napoli Federico II, P.le Tecchio, 80-80125 Napoli, Italy
Dipartimento Delle Scienze Biologiche, Università di Napoli Federico II, via Mezzocannone 16, 80134 Napoli, Italy
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Protein-protein interactions: a simple strategy to identify binding sites and peptide antagonists
Secondary structure motifs and small protein domains can act as building blocks that are isolated and investigated to gain insights into protein global structure but can also modulate interactions with external partners. Most progress has been made in this field using synthetic peptides. Fragmentation of folded proteins by proteolytic enzymes that act preferentially on exposed and less structured sites can help to isolate shorter polypeptides with preserved secondary and tertiary structures that mimic the original protein architecture. Such molecules can be used as probes for structural studies and as tools for in vitro assays to select active fragments useful as agonists or antagonists of the original protein or as scaffolds for the design of more potent and selective ligands. This simple but effective proteolytic methodology has been successfully applied to determine antagonists of protein-protein interactions, allowing the identification of inhibitors with high efficacy and specificity. Here, we present several studies including the complex between phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes and phospholipase 1, believed to play a relevant role in the insulin resistance mechanism in phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-overexpressing tissues, the self-association of BCL10 caspase recruitment domain that mediates a protein oligomerization process responsible for NF-kappaB activation and the self-association of growth arrest and DNA damage-inducible factor 45 beta, a major player of the endogenous NF-kappaB-mediated resistance to apoptosis.
Protein-protein interactions: a simple strategy to identify binding sites and peptide antagonists