The binary protein-protein interaction landscape of Escherichia coli
Open accessAbstract
Efforts to map the Escherichia coli interactome have identified several hundred macromolecular complexes, but direct binary protein-protein interactions (PPIs) have not been surveyed on a large scale. Here we performed yeast two-hybrid screens of 3,305 baits against 3,606 preys (∼70% of the E. coli proteome) in duplicate to generate a map of 2,234 interactions, which approximately doubles the number of known binary PPIs in E. coli. Integration of binary PPI and genetic-interaction data revealed functional dependencies among components involved in cellular processes, including envelope integrity, flagellum assembly and protein quality control. Many of the binary interactions that we could map in multiprotein complexes were informative regarding internal topology of complexes and indicated that interactions in complexes are substantially more conserved than those interactions connecting different complexes. This resource will be useful for inferring bacterial gene function and provides a draft reference of the basic physical wiring network of this evolutionarily important model microbe.
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There are currently 64,006 pairwise human protein interactions in the human reference interactome.
“There are currently 64,006 pairwise human protein interactions in the human reference interactome36.”
From Improved prediction of protein-protein interactions using AlphaFold2 (2021) · cites this paper as [36]
The Results section reports counts for the E. coli interactome, not a human reference interactome. Searches for “64,006 pairwise human protein interactions” and “human reference interactome” found no passage in our copy giving the claimed human interaction count. (LLM, conf=0.76)
Experimental — accuracy not yet measuredE. coli has a scale-free PPI network with τ = 1.3, as estimated in the authors' recent work.
“E. coli, for example, also has a scale-free PPI network69 with τ = 1.3 as estimated by our recent work.70”
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Mapping the Protein–Protein Interactome Networks Using Yeast Two-Hybrid Screens
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- Authors
- Rajagopala, S. V., Sikorski, P., Kumar, A., Mosca, R., Vlasblom, J., Arnold, R., Franca-Koh, J., Pakala, S. B., Phanse, S., Ceol, A., Häuser, R., Siszler, G., Wuchty, S., Emili, A., Babu, M., Aloy, P., Pieper, R., & Uetz, P.
- Affiliations
- J. Craig Venter Institute (US)
- University of Regina (CA)
- Institute for Research in Biomedicine (ES)
- University of Toronto (CA)
- German Cancer Research Center (DE)
- National Institutes of Health (US)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Virginia Commonwealth University (US)
- Corresponding author
- Rajagopala, Seesandra V
- Babu, Mohan
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2014-02-23
- Volume
- 32
- Issue
- 3
- Pages
- 285-290
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4123855
- OpenAlex
- W2108102049
- Cited by
- 233
- References
- 48
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 20 · 2023: 18 · 2022: 16 · 2021: 19 · 2020: 16 · 2019: 17 · 2018: 24 · 2017: 20 · 2016: 22 · 2015: 24 · 2014: 15
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM079710, R01GM079710)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- Escherichia coli, protein-protein interaction, protein-protein interaction network, macromolecular complexes, genetic interactions, flagellum assembly, protein quality control, gene function prediction
- MeSH terms
- Two-Hybrid System Techniques, Protein Interaction Mapping, Escherichia coli Proteins, Proteomics, Protein Interaction Maps
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