Dataset Information

The role of charged surface residues in the binding ability of small hubs in protein-protein interaction networks.

ABSTRACT: Hubs are highly connected proteins in a protein-protein interaction network. Previous work has implicated disordered domains and high surface charge as the properties significant in the ability of hubs to bind multiple proteins. While conformational flexibility of disordered domains plays an important role in the binding ability of large hubs, high surface charge is the dominant property in small hubs. In this study, we further investigate the role of the high surface charge in the binding ability of small hubs in the absence of disordered domains. Using multipole expansion, we find that the charges are highly distributed over the hub surfaces. Residue enrichment studies show that the charged residues in hubs are more prevalent on the exposed surface, with the exception of Arg, which is predominantly found at the interface, as compared to non-hubs. This suggests that the charged residues act primarily from the exposed surface rather than the interface to affect the binding ability of small hubs. They do this through (i) enhanced intra-molecular electrostatic interactions to lower the desolvation penalty, (ii) indirect long - range intermolecular interactions with charged residues on the partner proteins for better complementarity and electrostatic steering, and (iii) increased solubility for enhanced diffusion-controlled rate of binding. Along with Arg, we also find a high prevalence of polar residues Tyr, Gln and His and the hydrophobic residue Met at the interfaces of hubs, all of which have the ability to form multiple types of interactions, indicating that the interfaces of hubs are optimized to participate in multiple interactions.

SUBMITTER: Patil A

PROVIDER: S-EPMC5036656 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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The role of charged surface residues in the binding ability of small hubs in protein-protein interaction networks.

Patil Ashwini A Nakamura Haruki H

Biophysics (Nagoya-shi, Japan) 20070721

Hubs are highly connected proteins in a protein-protein interaction network. Previous work has implicated disordered domains and high surface charge as the properties significant in the ability of hubs to bind multiple proteins. While conformational flexibility of disordered domains plays an important role in the binding ability of large hubs, high surface charge is the dominant property in small hubs. In this study, we further investigate the role of the high surface charge in the binding abili ...[more]

PMID: 27857564

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Project description:BackgroundIn the post-genomic era, a central and overarching question in the analysis of protein-protein interaction networks continues to be whether biological characteristics and functions of proteins such as lethality, physiological malfunctions and malignancy are intimately linked to the topological role proteins play in the network as a mathematical structure. One of the key features that have implicitly been presumed is the existence of hubs, highly connected proteins considered to play a crucial role in biological networks. We explore the structure of protein interaction networks of a number of organisms as metric spaces and show that hubs are non randomly positioned and, from a distance point of view, centrally located.ResultsBy analysing how the human functional protein interaction network, the human signalling network, Saccharomyces cerevisiae, Arabidopsis thaliana and Escherichia coli protein-protein interaction networks from various databases are distributed as metric spaces, we found that proteins interact radially through a central node, high degree proteins coagulate in the centre of the network, and those far away from the centre have low degree. We further found that the distribution of proteins from the centre is in some hierarchy of importance and has biological significance.ConclusionsWe conclude that structurally, protein interaction networks are mathematical entities that share properties between organisms but not necessarily with other networks that follow power-law. We therefore conclude that (i) if there are hubs defined by degree, they are not distributed randomly; (ii) zones closest to the centre of the network are enriched for critically important proteins and are also functionally very specialised for specific 'house keeping' functions; (iii) proteins closest to the network centre are functionally less dispensable and may present good targets for therapy development; and (iv) network biology requires its own network theory modelled on actual biological evidence and that simply adopting theories from the social sciences may be misleading.

Dataset Information

The role of charged surface residues in the binding ability of small hubs in protein-protein interaction networks.

Publications

The role of charged surface residues in the binding ability of small hubs in protein-protein interaction networks.

Similar Datasets

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