Structural coverage of the human interactome
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Abstract
Complex biological processes in cells are embedded in the interactome, representing the complete set of protein–protein interactions. Mapping and analyzing the protein structures are essential to fully comprehending these processes’ molecular details. Therefore, knowing the structural coverage of the interactome is important to show the current limitations. Structural modeling of protein–protein interactions requires accurate protein structures. In this study, we mapped all experimental structures to the reference human proteome. Later, we found the enrichment in structural coverage when complementary methods such as homology modeling and deep learning (AlphaFold) were included. We then collected the interactions from the literature and databases to form the reference human interactome, resulting in 117 897 non-redundant interactions. When we analyzed the structural coverage of the interactome, we found that the number of experimentally determined protein complex structures is scarce, corresponding to 3.95% of all binary interactions. We also analyzed known and modeled structures to potentially construct the structural interactome with a docking method. Our analysis showed that 12.97% of the interactions from HuRI and 73.62% and 32.94% from the filtered versions of STRING and HIPPIE could potentially be modeled with high structural coverage or accuracy, respectively. Overall, this paper provides an overview of the current state of structural coverage of the human proteome and interactome.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
ClinVar: improving access to variant interpretations and supporting evidence
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Highly accurate protein structure prediction for the human proteome
Tunyasuvunakool, K., Adler, J., Wu, Z., Green, T., Zielinski, M., Žídek, A., Bridgland, A., Cowie, A., Meyer, C., Laydon, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03828-1 · Cited by 3,025 · cited 1× · see citing works
“These regions often pose challenges in structural modeling, making it difficult to obtain high-quality models [48,49].”
BackgroundThe BioPlex network: a systematic exploration of the human interactome
Huttlin, E. L., Ting, L., Bruckner, R. J., Gebreab, F., Gygi, M. P., Szpyt, J., Tam, S., Zarraga, G., Colby, G., Baltier, K., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.043 · Cited by 1,425 · cited 1× · see citing works
“We reviewed interactome databases currently available online, including HuRI [15], STRING [9], BioPlex [5], BioGRID [14], HIPPIE [10], Interactome INSIDER [3], Interactome3D [4] hu.”
MethodImproved prediction of protein-protein interactions using AlphaFold2
Bryant, P., Pozzati, G., & Elofsson, A. (2021) · doi:10.1101/2021.09.15.460468 · Cited by 1,025 · see citing works
A structural biology community assessment of AlphaFold2 applications
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AlphaFold and Implications for Intrinsically Disordered Proteins
Ruff, K. M., & Pappu, R. V. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167208 · Cited by 635 · see citing works
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Predicting Protein–Protein Interactions from the Molecular to the Proteome Level
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Towards a structurally resolved human protein interaction network
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The structural coverage of the human proteome before and after AlphaFold
Porta-Pardo, E., Ruiz-Serra, V., Valentini, S., & Valencia, A. (2022) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1009818 · Cited by 131 · see citing works
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- Authors
- Kosoglu, K., Aydin, Z., Tuncbag, N., Gursoy, A., & Keskin, O.
- Affiliations
- Koç University (TR)
- School of Medicine, Koc University , 34450 Istanbul , Turkey
- Department of Computer Engineering, College of Engineering, Koc University , 34450 Istanbul , Turkey
- Department of Chemical and Biological Engineering, College of Engineering, Koc University , 34450 Istanbul , Turkey
- Venue
- Briefings in Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-11-22
- Volume
- 25
- Issue
- 1
- ISSN
- 1467-5463 (ISSN-L)
- 1477-4054
- PMC
- PMC10768791
- OpenAlex
- W4390621084
- Cited by
- 21
- References
- 12
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 5
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Briefings in Bioinformatics (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Scientific and Technological Research Council of Turkey (120C120)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- human interactome, protein-protein interaction, structural coverage, protein structure mapping, protein complex structure, homology modeling, AlphaFold, molecular docking, strings, hippies, binary interaction
- MeSH terms
- Humans, Databases, Factual, Proteome
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