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

Frontiers in Bioengineering and Biotechnology

Alessandro eGiuliani¹  Gabriele eOliva²  Luisa eDi Paola²  Roberto eSetola²  Chiara Bianca Maria Platania³  Federica ePascucci⁴ 

[1] Istituto Superiore di Sanità;University of Campus Biomedico di Roma;University of Catania;Università degli Studi Roma Tre;

关键词: Proteins;    protein-protein interactions;    network resilience;    Anthrax toxin;    Protein Contact Networks;   

DOI  :  10.3389/fbioe.2015.00170

来源: DOAJ

【 摘 要 】

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 thestability 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.

【 授权许可】

Unknown