title: Protein intrinsic disorder and network connectivity. The case of 14-3-3 proteins.
abstract: The understanding of networks is a common goal of an unprecedented array of traditional disciplines. One of the protein network properties most influenced by the structural contents of its nodes is the inter-connectivity. Recent studies in which structural information was included into the topological analysis of protein networks revealed that the content of intrinsic disorder in the nodes could modulate the network topology, rewire networks, and change their inter-connectivity, which is defined by its clustering coefficient. Here, we review the role of intrinsic disorder present in the partners of the highly conserved 14-3-3 protein family on its interaction networks. The 14-3-3s are phospho-serine/threonine binding proteins that have strong influence in the regulation of metabolism and signal transduction networks. Intrinsic disorder increases the clustering coefficients, namely the inter-connectivity of the nodes within each 14-3-3 paralog networks. We also review two new ideas to measure intrinsic disorder independently of the primary sequence of proteins, a thermodynamic model and a method that uses protein structures and their solvent environment. This new methods could be useful to explain unsolved questions about versatility and fixation of intrinsic disorder through evolution. The relation between the intrinsic disorder and network topologies could be an interesting model to investigate new implicitness of the graph theory into biology.
authors.affiliation: Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico de Chascomús, Universidad Nacional de San Martín - Consejo Nacional de Investigaciones Científicas y Técnicas Chascomús, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: Uhart
authors.affiliation: Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico de Chascomús, Universidad Nacional de San Martín - Consejo Nacional de Investigaciones Científicas y Técnicas Chascomús, Argentina.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Bustos
keywords: 14-3-3 protein family; post-translational modifications; protein interaction networks; protein intrinsic disorder; protein phosphorylation