Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins
| العنوان: | Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins |
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| المؤلفون: | Negin Karimi Nasseri, Nazila Nazemof, Alberto Paccanaro, Pingzhao Hu, Peter D Wong, Shamanta Chandran, Gabriel Moreno-Hagelsieb, Gareth Butland, Anaies Nazarians-Armavil, Mehrab Ali, Ashkan Golshani, Wenhong Yang, Constantine C. Christopoulos, Jack Greenblatt, Sarath Chandra Janga, Xinghua Guo, Sadhna Phanse, Oxana Pogoutse, J. Javier Díaz-Mejía, Veronika Eroukova, Gabriel Musso, Andrew Emili, Mohan Babu |
| المصدر: | PLoS Biology, Vol 7, Iss 4, p e96 (2009) PLoS Biology, 7 (4) PLoS Biology Scopus-Elsevier |
| بيانات النشر: | Public Library of Science (PLoS), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Proteome, QH301-705.5, Biology, Faculty of Science\Computer Science, medicine.disease_cause, Genome, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Protein–protein interaction, 03 medical and health sciences, Phylogenetics, Protein Interaction Mapping, Protein biosynthesis, medicine, Escherichia coli, Biology (General), Gene, 030304 developmental biology, Genetics, 0303 health sciences, Evolutionary Biology, General Immunology and Microbiology, General Neuroscience, Escherichia coli Proteins, 030302 biochemistry & molecular biology, Bacterial, Computational Biology, Genetics and Genomics, Multiprotein Complexes, General Agricultural and Biological Sciences, Functional genomics, Genome, Bacterial, Research Article, Biotechnology |
| الوصف: | One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans' biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a “systems-wide” functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins. Author Summary One goal of modern biology is to chart groups of proteins that act together to perform biological processes via direct and indirect interactions. Such groupings are sometimes called functional modules. The types of protein interactions within modules include physical interactions that generate protein complexes and biochemical associations that make up metabolic pathways. We have combined proteomic and bioinformatic tools, and used them to decipher a large number of protein interactions, complexes, and functional modules with high confidence. In addition, exploring the topology of the resulting interaction networks, we successfully predicted specific biological roles for a number of proteins with previously unknown functions, and identified some potential drug targets. Although our work is focused on E. coli, our phylogenetic projections suggest that a considerable fraction of our observations and predictions can be extrapolated to many other bacterial taxa. As all the data derived from this study are publicly available, others may build on our work for further hypothesis-driven studies of gene function discovery. A novel resource integrating proteomic and genome context-based tools provides a "systems-wide" functional blueprint ofE. coli, with insights into the biological and evolutionary significance of previously uncharacterized proteins. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1545-7885 1544-9173 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d92c6bdaf27a8ad16aca01e41a4c718 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19402753/?tool=EBI |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5d92c6bdaf27a8ad16aca01e41a4c718 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15457885 15449173 |
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