Protein interface conservation across structure space
Open accessAbstract
With the advent of Systems Biology, the prediction of whether two proteins form a complex has become a problem of increased importance. A variety of experimental techniques have been applied to the problem, but three-dimensional structural information has not been widely exploited. Here we explore the range of applicability of such information by analyzing the extent to which the location of binding sites on protein surfaces is conserved among structural neighbors. We find, as expected, that interface conservation is most significant among proteins that have a clear evolutionary relationship, but that there is a significant level of conservation even among remote structural neighbors. This finding is consistent with recent evidence that information available from structural neighbors, independent of classification, should be exploited in the search for functional insights. The value of such structural information is highlighted through the development of a new protein interface prediction method, PredUs, that identifies what residues on protein surfaces are likely to participate in complexes with other proteins. The performance of PredUs, as measured through comparisons with other methods, suggests that relationships across protein structure space can be successfully exploited in the prediction of protein-protein interactions.
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- Authors
- Zhang, Q. C., Petrey, D., Norel, R., & Honig, B. H.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-06
- Volume
- 107
- Issue
- 24
- Pages
- 10896-10901
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2890749
- OpenAlex
- W2021703339
- Cited by
- 156
- References
- 38
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 11 · 2017: 11 · 2016: 8 · 2015: 19 · 2014: 13 · 2013: 17 · 2012: 25
- FWCI
- 7.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (CA121852, GM074958, GM030518)
- National Cancer Institute (U54CA121852, CA121852.)
- National Institute of General Medical Sciences (U54GM074958, R01GM030518, GM030518, R37GM030518, GM074958)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- protein-protein interaction prediction, protein binding sites, protein structure space, protein complexes, protein surface residues, phylogenetic relationships
- MeSH terms
- Binding Sites, Models, Molecular, Proteins, Sequence Alignment, Conserved Sequence, Protein Interaction Mapping, Databases, Protein, Structural Homology, Protein, Multiprotein Complexes, Systems Biology, Protein Interaction Domains and Motifs
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