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Protein-protein binding selectivity and network topology constrain global and local properties of interface binding networks
Author(s) -
David O. Holland,
Benjamin H. Shapiro,
Pei Xue,
Margaret E. Johnson
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-05686-2
Subject(s) - complementarity (molecular biology) , computational biology , binding site , network topology , protein–protein interaction , topology (electrical circuits) , interface (matter) , biology , computer science , genetics , mathematics , computer network , pulmonary surfactant , biochemistry , gibbs isotherm , combinatorics
Protein-protein interactions networks (PPINs) are known to share a highly conserved structure across all organisms. What is poorly understood, however, is the structure of the child interface interaction networks (IINs), which map the binding sites proteins use for each interaction. In this study we analyze four independently constructed IINs from yeast and humans and find a conserved structure of these networks with a unique topology distinct from the parent PPIN. Using an IIN sampling algorithm and a fitness function trained on the manually curated PPINs, we show that IIN topology can be mostly explained as a balance between limits on interface diversity and a need for physico-chemical binding complementarity. This complementarity must be optimized both for functional interactions and against mis-interactions, and this selectivity is encoded in the IIN motifs. To test whether the parent PPIN shapes IINs, we compared optimal IINs in biological PPINs versus random PPINs. We found that the hubs in biological networks allow for selective binding with minimal interfaces, suggesting that binding specificity is an additional pressure for a scale-free-like PPIN. We confirm through phylogenetic analysis that hub interfaces are strongly conserved and rewiring of interactions between proteins involved in endocytosis preserves interface binding selectivity.

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