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CHARACTERIZATION OF PROTEIN-PROTEIN INTERFACES THROUGH A PROTEIN-CONTACT-NETWORK APPROACH

By Luisa eDi Paola, Chiara Bianca Maria Platania, Gabriele eOliva, Roberto eSetola, Federica ePascucci and Alessandro eGiuliani

Abstract

Anthrax toxin comprises of three different proteins, jointly acting to exert toxic activity: a non-toxic protective agent (PA), toxic edema factor (EF) and lethal factor (LF). Binding of PA to anthrax receptors promotes oligomerization of PA, binding of EF and LF, then endocytosis of the complex. Homomeric forms of PA, complexes of PA bound to LF and to the endogenous receptor capillary morphogenesis gene 2 (CMG2) were analyzed. In this work, we characterized protein-protein interfaces (PPIs) and identified key residues at PPIs of complexes, by means of a protein contact network (PCN) approach. Flexibility, global and local topological properties of each PCN were computed. The vulnerability of each PCN was calculated using different node removal strategies, with reference to specific PCN topological descriptors: participation coefficient, contact order and degree. The participation coefficient P, the topological descriptor of the node’s ability to intervene in protein inter-module communication, was the key descriptor of PCN vulnerability of all structures. High P residues were localized both at PPIs and other regions of complexes, so that we argued an allosteric mechanism in protein-protein interactions. The identification of residues, with key role in the stability of PPIs, has a huge potential in the development of new drugs; which would be designed to target not only PPIs but also residues localized in allosteric regions of supramolecular complexes

Topics: Proteins, protein-protein interactions, network resilience, Anthrax toxin, Protein Contact Networks, Biotechnology, TP248.13-248.65
Publisher: Frontiers Media S.A.
Year: 2015
DOI identifier: 10.3389/fbioe.2015.00170
OAI identifier: oai:doaj.org/article:cc968e5ac215486bb4a0b2684bf8edbc
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