Abstract
Understanding protein functional interactions is an important research focus in the post-genomic era. The identification of interacting motif pairs is essential for exploring the mechanism of protein interactions. We describe a wordcounting approach for discovering motif pairs from known interactions and pairs of proteins that are putatively not to interact. Our interacting motif pairs are validated by multiple-chain PDB structures and motif pairs extracted from PDB structures. The motif pairs are used to predict interactions between proteins by three different methods. For all the methods used, our predicted protein-protein interactions significantly overlap with the experimental physical interactions. Furthermore, the mean correlation coefficients of the gene expression profiles for our predicted protein pairs are significantly higher than that for random pairs. Supplementary materials are available online at http://ctb.pku.edu.cn/∼yuhuan.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Altschul SF, Madden TL, Schaffer AA et al (1997) Gapped BLAST and PSIBLAST:a new generation of protein database search programs. Nucleic Acids Res 25 (17):3389–3402.
Alfarano C, Andrade CE, Anthony K et al (2005) The Biomolecular Interaction Network Database and related tools 2005 update. Nucleic Acids Res 33 (database issue):D418-D424.
Bock JR, Gough DA (2001) Predicting protein-protein interactions from primary structure. Bioinformatics 17 (5):455–460.
Boulton SJ, Gartner A, Reboul J et al (2002) Combined Functional Genomic Maps of the C. elegans DNA Damage Response. Science 295 (5552):127–131.
Breitkreutz BJ, Stark C, Tyers M (2003) The GRID:the General Repository for Interaction Datasets. Genome Biol 4 (3):R23.
Dandekar T, Snel B, Huynen M, Bork P (1998) Conservation of gene order:a fingerprint of proteins that physically interact. Trends Biochem Sci 23 (9):324–328.
Deng M, Mehta S, Sun F, Chen T (2002) Inferring Domain-Domain Interactions From Protein-Protein Interactions. Genome Res 12 (10):1540–1548.
Deng M, Sun F, Chen T (2003) Assessment of the reliability of protein-protein interactions and protein function prediction. Pac Symp Biocomput 2003:140–151.
Deshpande N, Addess KJ, Bluhm WF et al (2005) The RCSB Protein Data Bank:a redesigned query system and relational database based on the mmCIF schema. Nucleic Acids Res 33 (database issue):D233-D237.
Enright AJ, Iliopoulos I, Kyrpides NC, Ouzounis CA (1999) Protein interaction maps for complete genomes based on gene fusion events. Nature 402 (6757):86–90.
Falquet L, Pagni M, Bucher P et al (2002) The PROSITE database, its status in 2002. Nucleic Acids Res 30 (1):235–238.
Fields S, Song O (1989) A novel genetic system to detect protein-protein interactions. Nature 340 (6230):245–246.
Formstecher E, Aresta S, Collura V et al (2005) Protein interaction mapping:A Drosophila case study. Genome Res 15 (3):376–384.
Gavin AC, Bösche M, Krause R et al (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415 (6868):141–147.
Ge H, Liu Z, Church GM, Vidal M (2001) Correlation between transcriptome and interactome mapping data from Saccharomyces cerevisiae. Nat Genet 29 (4):482–486.
Giot L, Bader JS, Brouwer C et al (2003) A Protein Interaction Map of Drosophila melanogaster. Science 302 (5651):1727–1736.
Gomez SM, Lo SH, Rzhetsky A (2001) Probabilistic Prediction of Unknown Metabolic and Signal-Transduction Networks. Genetics 159 (3):1291–1298.
Gomez SM, Rzhetsky A (2002) Towards prediction of complete protein-protein interaction networks. Pac Symp Biocomput 2002:413–424.
Gomez SM, Noble WS, Rzhetsky A (2003) Learning to predict protein-protein interactions from protein sequences. Bioinformatics 19 (15):1875–1881.
Grigoriev A (2001) A relationship between gene expression and protein interactions on the proteome scale:analysis of the bacteriophage T7 and the yeast Saccharomyces cerevisiae. Nucleic Acids Res 29 (17):3513–3519.
Hazbun TR, Fields S (2001) Networking proteins in yeast. Proc Natl Acad Sci USA 98 (8):4277–4278.
Hayashida M, Ueda N, Akutsu T (2003) Inferring strengths of protein-protein interactions from experimental data using linear programming. Bioinformatics 19 (suppl 2):ii58-ii65.
Hermjakob H, Montecchi-Palazzi L, Lewington C et al (2004) IntAct:an open source molecular interaction database. Nucleic Acids Res 32 (database issue):D452-D455.
Ho Y, Gruhler A, Heilbut A et al (2002) Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415 (6868):180–183.
Huynen MA, Bork P (1998) Measuring genome evolution. Proc Natl Acad Sci USA 95 (11):5849–5856.
Ito T, Chiba T, Ozawa R, Yoshida M, Hattori M, Sakaki Y (2001) A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci USA 98 (8):4569–4574.
Jansen R, Greenbaum D, Gerstein M (2002) Relating Whole-Genome Expression Data with Protein-Protein Interactions. Genome Res 12 (1):37–46.
Kim WK, Park J, Suh JK (2002) Large scale co-evolution analysis of Protein Structural Interlogues using the global Protein Structural Interactome Map (PSIMAP). Genome Inform Ser Workshop Genome Inform 13:42–50.
Li S, Armstrong CM, Bertin N et al (2004) A Map of the Interactome Network of the Metazoan C. elegans. Science 303 (5657):540–543.
Li H, Li J, Tan SH, Ng SK (2004) Discovery of binding motif pairs from protein complex structural data and protein interaction sequence data. Pac Symp Biocomput 2004:312–323.
Li H, Li J (2005) Discovery of stable and significant binding motif pairs from PDB complexes and protein interaction datasets. Bioinformatics 21 (3):314–324.
MacBeath G, Schreiber SL (2000) Printing Proteins as Microarrays for High-Throughput Function Determination. Science 289 (5485):1760–1763.
Marcotte EM, Pellegrini M, Ng HL, Rice DW, Yeates TO, Eisenberg D (1999) Detecting Protein Function and Protein-Protein Interactions from Genome Sequences. Science 285 (5428):751–753.
Martin S, Roe D, Faulon JL (2005) Predicting protein-protein interactions using signature products. Bioinformatics 21 (2):218–226.
McCraith S, Holtzman T, Moss B, Fields S (2000) Genome-wide analysis of vaccinia virus protein-protein interactions. Proc Natl Acad Sci USA 97 (9):4879–4884.
Mewes HW, Frishman D, Güldener U et al (2002) MIPS:a database for genomes and protein sequences. Nucleic Acids Res 30 (1):31–34.
von Mering C, Jensen LJ, Snel B et al (2005) STRING:known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res 33 (database issue):D433-D437.
Mrowka R, Patzak A, Herzel H (2001) Is There a Bias in Proteome Research? Genome Res 11 (12):1971–1973.
Ng SK, Zhang Z, Tan SH (2003) Integrative approach for computationally inferring protein domain interactions. Bioinformatics 19 (8):923–929.
Overbeek R, Fonstein M, D'Souza M, Pusch GD, Maltsev N (1999) The use of gene clusters to infer functional coupling. Proc Natl Acad Sci USA 96 (6):2896–2901.
Pellegrini M, Marcotte EM, Thompson MJ, Eisenberg D, Yeates TO (1999) Assigning protein functions by comparative genome analysis:Protein phylogenetic profiles. Proc Natl Acad Sci USA 96 (8):4285–4288.
Phizicky EM, Fields S (1995) Protein-protein interactions:methods for detection and analysis. Microbiol Rev 59 (1):94–123.
Rain JC, Selig L, Reuse HD et al (2001) The protein-protein interaction map of Helicobacter pylori. Nature 409 (6820):211–215.
Salwinski L, Miller CS, Smith AJ, Pettit FK, Bowie JU, Eisenberg D (2004) The Database of Interacting Proteins:2004 update. Nucleic Acids Res 32 (database issue):D449-D451.
Spellman PT, Sherlock G, Zhang MQ et al (1998) Comprehensive Identification of Cell Cycle-regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization. Mol Bio Cell 9 (12):3273–3297.
Sprinzak E, Margalit H (2001) Correlated Sequence-signatures as Markers of Protein-Protein Interaction. J Mol Biol 311 (4):681–692.
Stanyon CA, Liu G, Mangiola BA et al (2004) A Drosophila protein-interaction map centered on cell-cycle regulators. Genome Biol 5 (12):R96.
Suzuki H, Fukunishi Y, Kagawa I et al (2001) Protein-Protein Interaction Panel Using Mouse Full-Length cDNAs. Genome Res 11 (10):1758–1765.
Uetz P, Giot L, Cagney G et al (2000) A comprehensive analysis of proteinprotein interactions protein-protein interactions in Saccharomyces cerevisiae in Saccharomyces. Nature 403 (6770):623–627.
Walhout AJ, Sordella R, Lu X et al (2000) Protein Interaction Mapping in C. elegans Using Proteins Involved in Vulval Development. Science 287 (5450):116–122.
Wang H, Segal E, Ben-Hur A, Koller D, Brutlag DL (2004) Identifying proteinprotein interaction sites on a genome-wide scale. In:Saul LK, Weiss Y, Bottou L (eds) Advances in Neural Information Processing Systems 17. MIT Press, Cambridge, MA.
Wojcik J, Schachter V (2001) Protein-protein interaction map inference using interacting domain profile pairs. Bioinformatics 17 (Suppl 1):S296-S305.
Liu Y, Liu N, Zhao H (2005) Inferring protein-protein interactions through high-throughput interaction data from diverse organisms. Bioinformatics 21 (15):3279–3285.
Zanzoni A, Montecchi-Palazzi L, Quondam M, Ausiello G, Helmer-Citterich M, Cesareni G (2002) MINT:a Molecular INTeraction database. FEBS Lett 513 (1):135–140.
Zhu H, Bilgin M, Bangham R et al (2001) Global Analysis of Protein Activities Using Proteome Chips. Science 293 (5537):2101–2105.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer
About this chapter
Cite this chapter
Yu, H., Qian, M., Deng, M. (2007). Understanding Protein-Protein Interactions: From Domain Level to Motif Level. In: Feng, J., Jost, J., Qian, M. (eds) Networks: From Biology to Theory. Springer, London. https://doi.org/10.1007/978-1-84628-780-0_11
Download citation
DOI: https://doi.org/10.1007/978-1-84628-780-0_11
Publisher Name: Springer, London
Print ISBN: 978-1-84628-485-4
Online ISBN: 978-1-84628-780-0
eBook Packages: Computer ScienceComputer Science (R0)