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Characterization of Protein–Protein Interfaces through a Protein Contact Network Approach

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....

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Autores principales: Di Paola, Luisa, Platania, Chiara Bianca Maria, Oliva, Gabriele, Setola, Roberto, Pascucci, Federica, Giuliani, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626657/
https://www.ncbi.nlm.nih.gov/pubmed/26579512
http://dx.doi.org/10.3389/fbioe.2015.00170
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author Di Paola, Luisa
Platania, Chiara Bianca Maria
Oliva, Gabriele
Setola, Roberto
Pascucci, Federica
Giuliani, Alessandro
author_facet Di Paola, Luisa
Platania, Chiara Bianca Maria
Oliva, Gabriele
Setola, Roberto
Pascucci, Federica
Giuliani, Alessandro
author_sort Di Paola, Luisa
collection PubMed
description 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.
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spelling pubmed-46266572015-11-17 Characterization of Protein–Protein Interfaces through a Protein Contact Network Approach Di Paola, Luisa Platania, Chiara Bianca Maria Oliva, Gabriele Setola, Roberto Pascucci, Federica Giuliani, Alessandro Front Bioeng Biotechnol Bioengineering and Biotechnology 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. Frontiers Media S.A. 2015-10-30 /pmc/articles/PMC4626657/ /pubmed/26579512 http://dx.doi.org/10.3389/fbioe.2015.00170 Text en Copyright © 2015 Di Paola, Platania, Oliva, Setola, Pascucci and Giuliani. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Di Paola, Luisa
Platania, Chiara Bianca Maria
Oliva, Gabriele
Setola, Roberto
Pascucci, Federica
Giuliani, Alessandro
Characterization of Protein–Protein Interfaces through a Protein Contact Network Approach
title Characterization of Protein–Protein Interfaces through a Protein Contact Network Approach
title_full Characterization of Protein–Protein Interfaces through a Protein Contact Network Approach
title_fullStr Characterization of Protein–Protein Interfaces through a Protein Contact Network Approach
title_full_unstemmed Characterization of Protein–Protein Interfaces through a Protein Contact Network Approach
title_short Characterization of Protein–Protein Interfaces through a Protein Contact Network Approach
title_sort characterization of protein–protein interfaces through a protein contact network approach
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626657/
https://www.ncbi.nlm.nih.gov/pubmed/26579512
http://dx.doi.org/10.3389/fbioe.2015.00170
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