Competition-cooperation relationship networks characterize the competition and cooperation between proteins.

Hong Li,Yuan Zhou,Ziding Zhang

doi:10.1038/srep11619

Hong Li, Yuan Zhou + Show 1 more

Open Access

https://doi.org/10.1038/srep11619

Copy DOI

Journal: Scientific Reports	Publication Date: Jun 25, 2015
Citations: 4	License type: CC BY 4.0

Affiliation: China Agricultural University

Abstract

By analyzing protein-protein interaction (PPI) networks, one can find that a protein may have multiple binding partners. However, it is difficult to determine whether the interactions with these partners occur simultaneously from binary PPIs alone. Here, we construct the yeast and human competition-cooperation relationship networks (CCRNs) based on protein structural interactomes to clearly exhibit the relationship (competition or cooperation) between two partners of the same protein. If two partners compete for the same interaction interface, they would be connected by a competitive edge; otherwise, they would be connected by a cooperative edge. The properties of three kinds of hubs (i.e., competitive, modest, and cooperative hubs) are analyzed in the CCRNs. Our results show that competitive hubs have higher clustering coefficients and form clusters in the human CCRN, but these tendencies are not observed in the yeast CCRN. We find that the human-specific proteins contribute significantly to these differences. Subsequently, we conduct a series of computational experiments to investigate the regulatory mechanisms that avoid competition between proteins. Our comprehensive analyses reveal that for most yeast and human protein competitors, transcriptional regulation plays an important role. Moreover, the human-specific proteins have a particular preference for other regulatory mechanisms, such as alternative splicing.

Highlights

Protein-protein interaction (PPI) networks have been integrated with various data in order to provide a systematic understanding of diverse biological processes[10,11]
If two proteins interact with a common protein through the same interaction interface, they are defined as a competitive pair connected by a competitive edge
We constructed a human competition-cooperation relationship networks (CCRNs) containing 2,897 proteins connected by 10,463 competitive edges and 11,048 cooperative edges (Fig. 1; the raw network data of the CCRNs and the full list of their edges are available at http://systbio.cau.edu.cn/CCRN/)

Summary

Introduction

PPI networks have been integrated with various data in order to provide a systematic understanding of diverse biological processes[10,11]. The interface-interaction network provides detailed information regarding individual interfaces, which is important for protein engineering and drug design. It does not provide a straightforward way to analyze how extensive competition is regulated in vivo, because most of the related data (e.g., the gene expression data and the alternative splicing information) do not describe interfaces but rather proteins or genes. We combine PPI networks with protein structure data to construct the yeast and human competition-cooperation relationship networks (CCRNs; Fig. 1). We ascribe these differences mainly to the emergence of human-specific proteins. We find that the human-specific proteins are regulated in a distinct fashion in which intensive competitive interactions are avoided

Methods

Results

Discussion

Conclusion