title: Linear motif-mediated interactions have contributed to the evolution of modularity in complex protein interaction networks.
abstract: The modular architecture of protein-protein interaction (PPI) networks is evident in diverse species with a wide range of complexity. However, the molecular components that lead to the evolution of modularity in PPI networks have not been clearly identified. Here, we show that weak domain-linear motif interactions (DLIs) are more likely to connect different biological modules than strong domain-domain interactions (DDIs). This molecular division of labor is essential for the evolution of modularity in the complex PPI networks of diverse eukaryotic species. In particular, DLIs may compensate for the reduction in module boundaries that originate from increased connections between different modules in complex PPI networks. In addition, we show that the identification of biological modules can be greatly improved by including molecular characteristics of protein interactions. Our findings suggest that transient interactions have played a unique role in shaping the architecture and modularity of biological networks over the course of evolution.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Inhae
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Heetak
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Seong Kyu
authors.initials: SK
authors.lastname: Han
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D060066:Protein Interaction Maps / Q000502:physiology*; D017434:Protein Structure, Tertiary