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Protein–protein interaction networks: how can a hub protein bind so many different partners?
Open accessAbstract
How can a single hub protein bind so many different partners? Numerous studies have sought differences between hubs and non-hubs to explain what makes a protein a hub and how a shared hub-binding site can be promiscuous, yet at the same time be specific. Here, we suggest that the problem is largely non-existent and resides in the popular representation of protein interaction networks: protein products derived from a single gene, even if different, are clustered in maps into a single node. This leads to the impression that a single protein binds to a very large number of partners. In reality, it does not; rather, protein networks reflect the combination of multiple proteins, each with a distinct conformation.
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“This mechanism appears to be in addition to other mechanisms adopted by hub proteins, such as covalent linkage to protein interaction domains, alternative splicing variants, etc.524”
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 [524]
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Cites
Emergence of Scaling in Random Networks
Barabási, A.-L., & Albert, R. (1999) · Science · doi:10.1126/science.286.5439.509 · Cited by 36,135
Finishing the euchromatic sequence of the human genome
International Human Genome Sequencing Consortium (2004) · Nature · doi:10.1038/nature03001 · Cited by 4,971
Functional organization of the yeast proteome by systematic analysis of protein complexes
Gavin, A., Böesche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A., Cruciat, C., et al. (2002) · Nature · doi:10.1038/415141a · Cited by 4,729
A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae
Uetz, P., Giot, L., Cagney, G., Mansfield, T. A., Judson, R. S., Knight, J. R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., et al. (2000) · Nature · doi:10.1038/35001009 · Cited by 4,706
Network pharmacology: the next paradigm in drug discovery
Hopkins, A. L. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.118 · Cited by 4,622
Global landscape of protein complexes in the yeast Saccharomyces cerevisiae
Krogan, N. J., Cagney, G., Yu, H., Zhong, G., Guo, X., Ignatchenko, A., Li, J., Pu, S., Datta, N., Tikuisis, A., et al. (2006) · Nature · doi:10.1038/nature04670 · Cited by 2,969
A "Silent" Polymorphism in the MDR 1 Gene Changes Substrate Specificity
Kimchi-Sarfaty, C., Oh, J. M., Kim, I.-W., Sauna, Z. E., Calcagno, A. M., Ambudkar, S. V., & Gottesman, M. M. (2007) · Science · doi:10.1126/science.1135308 · Cited by 2,416
Evidence for dynamically organized modularity in the yeast protein–protein interaction network
Han, J. J., Bertin, N., Hao, T., Goldberg, D. S., Berriz, G. F., Zhang, L. V., Dupuy, D., Walhout, A. J. M., Cusick, M. E., Roth, F. P., et al. (2004) · Nature · doi:10.1038/nature02555 · Cited by 1,789
Flexible nets: The roles of intrinsic disorder in protein interaction networks
Dunker, A. K., Cortese, M. S., Romero, P., Iakoucheva, L. M., & Uversky, V. N. (2005) · The FEBS Journal · doi:10.1111/j.1742-4658.2005.04948.x · Cited by 1,122
Recognition Dynamics Up to Microseconds Revealed from an RDC-Derived Ubiquitin Ensemble in Solution
Lange, O. F., Lakomek, N., Farès, C., Schroeder, G. F., Walter, K. F. A., Becker, S., Meiler, J., Grubmüller, H., Griesinger, C., & de Groot, B. L. (2008) · Science · doi:10.1126/science.1157092 · Cited by 1,044
Why Do Hubs Tend to Be Essential in Protein Networks?
He, X., & Zhang, J. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020088 · Cited by 699
Principles of Protein−Protein Interactions: What are the Preferred Ways For Proteins To Interact?
Keskin, O., Gursoy, A., Ma, B., & Nussinov, R. (2008) · Chemical Reviews · doi:10.1021/cr040409x · Cited by 697
Self-citationFolding funnels, binding funnels, and protein function
Tsai, C., Kumar, S., Ma, B., & Nussinov, R. (1999) · Protein Science · doi:10.1110/ps.8.6.1181 · Cited by 648
Self-citationFolding and binding cascades: Dynamic landscapes and population shifts
Kumar, S., Ma, B., Tsai, C., Sinha, N., & Nussinov, R. (2000) · Protein Science · doi:10.1110/ps.9.1.10 · Cited by 595
Self-citationIntrinsic Disorder Is a Common Feature of Hub Proteins from Four Eukaryotic Interactomes
Haynes, C. A., Oldfield, C. J., Ji, F., Klitgord, N., Cusick, M. E., Predrag Radivojac, A., Uversky, V. N., Vidal, M., & Iakoucheva, L. M. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020100 · Cited by 593
The molecular sociology of the cell
Robinson, C. V., Šali, A., & Baumeister, W. P. (2007) · Nature · doi:10.1038/nature06523 · Cited by 553
Romero, P. R., Zaidi, S., Fang, Y. Y., Uversky, V. N., Radivojac, P., Oldfield, C. J., Cortese, M. S., Sickmeier, M., LeGall, T., Obradovic, Z., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507916103 · Cited by 480
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Kim, P. M., Lu, L. J., Xia, Y., & Gerstein, M. (2006) · Science · doi:10.1126/science.1136174 · Cited by 471
Dynamic Complex Formation During the Yeast Cell Cycle
de Lichtenberg, U., Jensen, L. J., Brunak, S., & Bork, P. (2005) · Science · doi:10.1126/science.1105103 · Cited by 405
Ekman, D. S., Light, S., Björklund, Å. K., & Elofsson, A. (2006) · Genome biology · doi:10.1186/gb-2006-7-6-r45 · Cited by 378
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Sakharkar, M. K., Chow, V. T. K., & Kangueane, P. (2004) · In Silico Biology: Journal of Biological Systems Modeling and Multi-Scale Simulation · doi:10.3233/isb-00142 · Cited by 328
Tsai, C., del Sol, A., & Nussinov, R. (2009) · Molecular BioSystems · doi:10.1039/b819720b · Cited by 324
Self-citationStein, L. D. (2004) · Nature · doi:10.1038/431915a · Cited by 309
Evolvability and hierarchy in rewired bacterial gene networks
Isalan, M., Lemerle, C., Michalodimitrakis, K., Horn, C., Beltrao, P., Raineri, E., Garriga-Canut, M., & Serrano, L. (2008) · Nature · doi:10.1038/nature06847 · Cited by 307 · cited 1×
“Networks, gene networks [1], residue networks [2-4], cellular networks [4,5], pharmacological networks [6,7], drug-therapy networks [8], functional networks [9-11] and, in particular, protein–protein interaction networks are the focus of intense research.”
BackgroundSynonymous Mutations and Ribosome Stalling Can Lead to Altered Folding Pathways and Distinct Minima
Tsai, C., Sauna, Z. E., Kimchi‐Sarfaty, C., Ambudkar, S. V., Gottesman, M. M., & Nussinov, R. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.08.012 · Cited by 256
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Hertel, K. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.r700035200 · Cited by 217
Lello, P. D., Jenkins, L. M. M., Jones, T. N., Nguyen, B. D., Hara, T. J., Yamaguchi, H., Dikeakos, J. D., Appella, E., Legault, P., & Omichinski, J. G. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.007 · Cited by 206
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Boxem, M., Maliga, Z., Klitgord, N., Li, N., Lemmens, I. H., Mana, M., de Lichtervelde, L., Mul, J. D., van de Peut, D., Devos, M., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.009 · Cited by 202
Boehr, D. D., & Wright, P. E. (2008) · Science · doi:10.1126/science.1158818 · Cited by 194
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Kruse, J.-P., & Gu, W. J. (2008) · Cell · doi:10.1016/j.cell.2008.05.020 · Cited by 183
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Thomas, D., Plant, L. D., Wilkens, C. M., McCrossan, Z. A., & Goldstein, S. A. N. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.016 · Cited by 151
Structural basis of Dscam isoform specificity
Meijers, R., Püettmann-Holgado, R., Skiniotis, G., Liu, J.-H., Walz, T., Wang, J., & Schmucker, D. (2007) · Nature · doi:10.1038/nature06147 · Cited by 150
Emerging roles of BRCA1 alternative splicing
Orbán, T. I., & Oláh, E. (2003) · Molecular Pathology · doi:10.1136/mp.56.4.191 · Cited by 145
Similar Binding Sites and Different Partners: Implications to Shared Proteins in Cellular Pathways
Keskin, O., & Nussinov, R. (2007) · Structure · doi:10.1016/j.str.2007.01.007 · Cited by 144
Self-citationCsermely, P. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.09.006 · Cited by 129
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Daily, M. D., & Gray, J. J. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000293 · Cited by 116
Keskin, Ö., Ma, B., Rogale, K., Gunasekaran, K., & Nussinov, R. (2005) · Physical Biology · doi:10.1088/1478-3975/2/2/s03 · Cited by 101
Self-citationToward accurate reconstruction of functional protein networks
Yosef, N., Ungar, L., Zalckvar, E., Kimchi, A., Kupiec, M., Ruppin, E., & Sharan, R. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.3 · Cited by 93
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Kwong, J., Hong, L., Liao, R., Deng, Q., Han, J., & Sun, P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808327200 · Cited by 85
Ghosh, A., & Vishveshwara, S. (2008) · Biochemistry · doi:10.1021/bi8007559 · Cited by 83
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Tunçbağ, N., Kar, G., Gürsoy, A., Keskin, Ö., & Nussinov, R. (2009) · Molecular BioSystems · doi:10.1039/b905661k · Cited by 78
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Yura, K., Shionyu, M., Hagino, K., Hijikata, A., Hirashima, Y., Nakahara, T., Eguchi, T., Shinoda, K., Yamaguchi, A., Takahashi, K.-I., et al. (2006) · Gene · doi:10.1016/j.gene.2006.05.015 · Cited by 70
Simkin, D., Cavanaugh, E. J., & Kim, D. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.161927 · Cited by 65
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Lätzer, J., Shen, T., & Wolynes, P. G. (2008) · Biochemistry · doi:10.1021/bi701350v · Cited by 57
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Tommasi, S., Pilato, B., Pinto, R., Monaco, A., Bruno, M., Campana, M., Digennaro, M., Schittulli, F., Lacalamita, R., & Paradiso, A. (2008) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2008.07.005 · Cited by 46
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Self-citationHonoré, É. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.165019 · Cited by 8
Ashworth, A. (2004) · Nature Cell Biology · doi:10.1038/ncb1004-916 · Cited by 8
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Metadata
- Authors
- Tsai, C.-J., Ma, B., & Nussinov, R.
- Affiliations
- National Cancer Institute (US)
- Tel Aviv University (IL)
- Corresponding author
- Nussinov, Ruth
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 34
- Issue
- 12
- Pages
- 594-600
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC7292551
- OpenAlex
- W1998203484
- Cited by
- 138
- References
- 57
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 8 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 14 · 2013: 22 · 2012: 12
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HHSN261200800001C)
- National Cancer Institute (Z01BC010440, HHSN261200800001E))
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- protein-protein interaction network, hub proteins, binding promiscuity, binding specificity, protein conformation, network representation, protein clustering
- MeSH terms
- Models, Biological, Protein Binding, Proteins
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