Disorder and Sequence Repeats in Hub Proteins and Their Implications for Network Evolution
Abstract
Protein interaction networks display approximate scale-free topology, in which hub proteins that interact with a large number of other proteins determine the overall organization of the network. In this study, we aim to determine whether hubs are distinguishable from other networked proteins by specific sequence features. Proteins of different connectednesses were compared in the interaction networks of Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, and Homo sapienswith respect to the distribution of predicted structural disorder, sequence repeats, low complexity regions, and chain length. Highly connected proteins ("hub proteins") contained significantly more of, and greater proportion of, these sequence features and tended to be longer overall as compared to less connected proteins. These sequence features provide two different functional means for realizing multiple interactions: (1) extended interaction surface and (2) flexibility and adaptability, providing a mechanism for the same region to bind distinct partners. Our view contradicts the prevailing view that scaling in protein interactomes arose from gene duplication and preferential attachment of equivalent proteins. We propose an alternative evolutionary network specialization process, in which certain components of the protein interactome improved their fitness for binding by becoming longer or accruing regions of disorder and/or internal repeats and have therefore become specialized in network organization.
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Disordered proteins account for a large fraction of all cellular proteins.
“Disordered proteins account for a large fraction of all cellular proteins.248”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [248]
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- Authors
- Dosztányi, Z., Chen, J., Dunker, A. K., Simon, I., & Tompa, P.
- Affiliations
- Indiana University Indianapolis (US)
- Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, 1518 Budapest, Hungary, School of Informatics, Indiana University, Indianapolis, Indiana 46202, Department of Computer and Information Science, Purdue School of Science, Indianapolis, Indiana 46202, and Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University, Indianapolis, Indiana 46202
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-10-06
- Volume
- 5
- Issue
- 11
- Pages
- 2985-2995
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W2143399071
- Cited by
- 341
- References
- 63
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 10 · 2023: 7 · 2022: 14 · 2021: 20 · 2020: 18 · 2019: 12 · 2018: 12 · 2017: 17 · 2016: 13 · 2015: 23 · 2014: 22 · 2013: 29 · 2012: 31
- FWCI
- 8.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (ISRF067595)
- U.S. National Library of Medicine (R01LM007688)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Complex Network Analysis Techniques
- Keywords
- hub proteins, protein-protein interaction network, intrinsically disordered proteins, sequence repeats, low complexity regions, network evolution, scale-free topology, protein length, protein flexibility, binding specificity, gene duplication, preferential attachment, Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, human
- MeSH terms
- Amino Acid Sequence, Animals, Drosophila melanogaster, Humans, Nerve Net, Proteins, Saccharomyces cerevisiae, Genome, Caenorhabditis elegans, Sequence Homology, Amino Acid, Evolution, Molecular, Repetitive Sequences, Amino Acid, Saccharomyces cerevisiae Proteins, Drosophila Proteins, Caenorhabditis elegans Proteins
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