title: Characterization of Protein-Protein Interfaces through a Protein Contact Network Approach.
abstract: Anthrax toxin comprises 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, and 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 and 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, such as 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.
authors.affiliation: Facoltà Dipartimentale di Ingegneria, Università Campus Bio-Medico di Roma , Rome , Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Di Paola
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania , Catania , Italy.
authors.forename: Chiara Bianca Maria
authors.initials: CB
authors.lastname: Platania
authors.affiliation: Facoltà Dipartimentale di Ingegneria, Università Campus Bio-Medico di Roma , Rome , Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Oliva
authors.affiliation: Facoltà Dipartimentale di Ingegneria, Università Campus Bio-Medico di Roma , Rome , Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Setola
authors.affiliation: Dipartimento di Informatica e Automazione, Università degli studi Roma Tre , Rome , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pascucci
authors.affiliation: Dipartimento di Ambiente e Connessa Prevenzione Primaria, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuliani
keywords: anthrax toxin; network resilience; protein contact networks; protein–protein interactions