The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“E. coli, for example, also has a scale-free PPI network69 with τ = 1.3 as estimated by our recent work.70”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196
Exploring Network Structure, Dynamics, and Function Using NetworkX
Hagberg, A. A., Schult, D. A., & Swart, P. J. (2008) · Proceedings of the Python in Science Conference · doi:10.25080/tcwv9851 · Cited by 7,477
Towards a proteome-scale map of the human protein–protein interaction network
Rual, J.-F. M., Venkatesan, K., Hao, T., Hirozane-Kishikawa, T., Dricot, A., Li, N., Berriz, G. F., Gibbons, F. D., Dreze, M., Ayivi-Guedehoussou, N., et al. (2005) · Nature · doi:10.1038/nature04209 · Cited by 2,904
Proteome survey reveals modularity of the yeast cell machinery
Gavin, A., Aloy, P., Grandi, P., Krause, R., Böesche, M., Marzioch, M., Rau, C., Jensen, L. J., Bastuck, S., Dümpelfeld, B., et al. (2006) · Nature · doi:10.1038/nature04532 · Cited by 2,570
Self-citationThe Genetic Landscape of a Cell
Costanzo, M., Baryshnikova, A., Bellay, J., Kim, Y., Spear, E. D., Sevier, C. S., Ding, H., Koh, J. L. Y., Toufighi, K., Mostafavi, S., et al. (2010) · Science · doi:10.1126/science.1180823 · Cited by 2,162
Scale-Free Networks: A Decade and Beyond
Barabási, A.-Ĺ. (2009) · Science · doi:10.1126/science.1173299 · Cited by 2,138
High-Quality Binary Protein Interaction Map of the Yeast Interactome Network
Yu, H., Braun, P., Yıldırım, M. A., Lemmens, I., Venkatesan, K., Sahalie, J., Hirozane-Kishikawa, T., Gebreab, F., Li, N., Simonis, N., et al. (2008) · Science · doi:10.1126/science.1158684 · Cited by 1,392
A new method to measure the semantic similarity of GO terms
Wang, J. Z., Du, Z., Payattakool, R., Yu, P. S., & Chen, C.-F. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm087 · Cited by 1,377
Interaction network containing conserved and essential protein complexes in Escherichia coli
Butland, G., Peregrín-Alvarez, J. M., Li, J., Yang, W., Yang, X., Canadien, V., Starostine, A., Richards, D., Beattie, B., Krogan, N., et al. (2005) · Nature · doi:10.1038/nature03239 · Cited by 1,201
Self-citationAutomatic clustering of orthologs and in-paralogs from pairwise species comparisons
Remm, M., Storm, C. E. V., & Sonnhammer, E. L. L. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.5197 · Cited by 1,175
Cited by
Sorted by citations
Items 201–232 of 232
Interactomes-Scaffolds of Cellular Systems
Luck, K., Jailkhani, N., Cusick, M. E., Rolland, T., Calderwood, M. A., Charloteaux, B., & Vidal, M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.40037-4 · Cited by 1
ZIPPI: proteome-scale sequence-based evaluation of protein-protein interaction modelsPreprint
Zhao, H., Petrey, D. S., Murray, D., & Honig, B. H. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.25.542344 · Cited by 1
Network-Based Analysis for Biological Knowledge Discovery
Tripathi, L. P., Osorio, R. S. A., Murakami, Y., Chen, Y. A., & Mizuguchi, K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95502-7.00272-4 · Cited by 1
Genome wide analyses of the Escherichia coli primary and secondary transcriptomes
Alvarez, D. R. (2014) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York)
Keasey, S. L., Natesan, M., Pugh, C. L., Kamata, T., Wuchty, S., & Ulrich, R. G. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m116.059337 · Cited by 1
Self-citationCuív, P. Ó., Burman, S., Pottenger, S., & Morrison, M. (2016) · Springer eBooks · doi:10.1007/978-3-319-46326-1_3 · Cited by 1
Network Analysis and Modeling in Systems Biology
Chacón, G. B. (2017) · RiuNet (Universitat Politècnica de València) · doi:10.4995/thesis/10251/79082
Computational Structural Biology of Macromolecular Interactions
Rodrigues, J. G. L. M. (2014) · Utrecht University Repository (Utrecht University)
Manikandan, P., & Ramyachitra, D. (2018) · IEEE/ACIS International Conference on Computer and Information Science (ICIS) · doi:10.1109/icis.2018.8466500
Bundalovic-Torma, C. (2018) · TSpace (University of Toronto)
Tetrameric UvrD helicase is located at the E. coli replisome due to frequent replication blocksPreprint
Wollman, A. J. M., Syeda, A. H., Howard, J. A. L., Payne-Dwyer, A. L., Leech, A., Warecka, D., Guy, C. P., McGlynn, P., Hawkins, M., & Leake, M. C. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.22.432310
Babu, M. M., & Li, X. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732738941.793545621
Self-citationXue, X., Chen, Z., Hu, Y., Nie, D., Zhao, H., & Mao, X. (2022) · FEBS Open Bio · doi:10.1002/2211-5463.13437
Protein Complexes in Bacillus subtilis by AI-Assisted Structural ProteomicsPreprint
O'Reilly, F. J., Graziadei, A., Forbrig, C., Bremenkamp, R., Charles, K., Lenz, S., Elfmann, C., Fischer, L., Stülke, J., & Rappsilber, J. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4186259
Wimble, C. (2015) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/thqh-m396
The protein interactome of the citrus Huanglongbing pathogen Candidatus Liberibacter asiaticusPreprint
Carter, E. W., Guerra‐Peraza, O., & Wang, N. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.10.548374
Fang, T., Szklarczyk, D., Hachilif, R., & von Mering, C. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.28.550005
Savvopoulou, V. A., & Klapa, M. I. (2024) · IFAC-PapersOnLine · doi:10.1016/j.ifacol.2024.10.009
Characterization of YdgH: a mediator of beta-lactam susceptibility in Enterobacterales
Lazarus, J. E., Waldor, M. K., & Hooper, D. C. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.01940-24
Decoding ATXN2 Phosphocode: Structural Insights and Therapeutic Opportunities in Disease
Kumar, A. P. K. A., Subair, S., Shivamurthy, P. B., Ummar, S., Rajeev, A. C., & Raju, R. (2025) · The Protein Journal · doi:10.1007/s10930-025-10287-4
Self-citationEssential Protein Identification Using FCNN and Harris Hawks Optimization
Bhuiyan, M. I. F., Nasir, N., Noman, M. A. A., Hossen, P., & Islam, M. R. (2026) · Applied Computational Intelligence and Soft Computing · doi:10.1155/acis/1243805
Comparing isotherm parameter determination methods for hydrophobic interaction chromatography
Neijenhuis, T., Vale, T. C. E., Bussy, O. L., Geldhof, G., Klijn, M. E., & Ottens, M. (2026) · Journal of Chromatography A · doi:10.1016/j.chroma.2026.466912
Functional flexibility in bacterial hub proteins is driven by proteome expansion
Paradžik, M., Prekpalaj, S., & Paradžik, T. (2026) · Scientific Reports · doi:10.1038/s41598-026-52986-7
Merighi, D. G. S., Pompeu, G. C., de Araujo, G. G., de Souza, A. S., Sgro, G. G., Farah, C. S., & Guzzo, C. R. (2026) · Structure · doi:10.1016/j.str.2026.05.009
Listing Minimal Cores in Large Real-World Graphs
Sun, Y., Yu, K., Liu, S., Long, C., Wong, R. C.-W., Zhou, X., & Zhang, M. (2026) · IEEE International Conference on Data Engineering (ICDE) · doi:10.1109/icde65706.2026.00190
Khan, N. A., Fahma, A., Gopalakrishnan, A. P., Sambreena, A., Raju, R., & Rajeev, A. C. (2026) · BioTech · doi:10.3390/biotech15040095
The Aminoacyl-tRNA Synthetases and Their Protein–Protein Interactions
Hendrickson, T. L., Bachert, N. P., Mack, G. F., Buzenski, N. W., & Lee, B. C. (2026) · Biomolecules · doi:10.3390/biom16111544
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review