Specificity and Commonality of the Phosphoinositide-Binding Proteome Analyzed by Quantitative Mass Spectrometry
Phosphoinositides (PIPs) play key roles in signaling and disease. Using high-resolution quantitative mass spectrometry, we identified PIP-interacting proteins and profiled their binding specificities toward all seven PIP variants. This analysis revealed 405 PIP-binding proteins, which is greater tha...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713007961 |
| _version_ | 1818152999379271680 |
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| author | Stephanie Jungmichel Kathrine B. Sylvestersen Chunaram Choudhary Steve Nguyen Matthias Mann Michael L. Nielsen |
| author_facet | Stephanie Jungmichel Kathrine B. Sylvestersen Chunaram Choudhary Steve Nguyen Matthias Mann Michael L. Nielsen |
| author_sort | Stephanie Jungmichel |
| collection | DOAJ |
| description | Phosphoinositides (PIPs) play key roles in signaling and disease. Using high-resolution quantitative mass spectrometry, we identified PIP-interacting proteins and profiled their binding specificities toward all seven PIP variants. This analysis revealed 405 PIP-binding proteins, which is greater than the total number of phospho- or ubiquitin-binding domains. Translocation and inhibitor assays of identified PIP-binding proteins confirmed that our methodology targets direct interactors. The PIP interactome encompasses proteins from diverse cellular compartments, prominently including the nucleus. Our data set revealed a consensus motif for PI(3,4,5)P3-interacting pleckstrin homology (PH) domains, which enabled in silico identification of phosphoinositide interactors. Members of the dedicator of cytokinesis family C exhibited specificity toward both PI(3,4,5)P3 and PI(4,5)P2. Structurally, this dual specificity is explained by a decreased number of positively charged residues in the L1 subdomain compared with DOCK1. The presented PIP-binding proteome and its specificity toward individual PIPs should be a valuable resource for the community. |
| first_indexed | 2024-12-11T14:03:38Z |
| format | Article |
| id | doaj.art-df5ab46dc08c49758e50efd0539431df |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T14:03:38Z |
| publishDate | 2014-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-df5ab46dc08c49758e50efd0539431df2022-12-22T01:03:45ZengElsevierCell Reports2211-12472014-02-016357859110.1016/j.celrep.2013.12.038Specificity and Commonality of the Phosphoinositide-Binding Proteome Analyzed by Quantitative Mass SpectrometryStephanie Jungmichel0Kathrine B. Sylvestersen1Chunaram Choudhary2Steve Nguyen3Matthias Mann4Michael L. Nielsen5Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkDepartment of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried 82152, GermanyDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkPhosphoinositides (PIPs) play key roles in signaling and disease. Using high-resolution quantitative mass spectrometry, we identified PIP-interacting proteins and profiled their binding specificities toward all seven PIP variants. This analysis revealed 405 PIP-binding proteins, which is greater than the total number of phospho- or ubiquitin-binding domains. Translocation and inhibitor assays of identified PIP-binding proteins confirmed that our methodology targets direct interactors. The PIP interactome encompasses proteins from diverse cellular compartments, prominently including the nucleus. Our data set revealed a consensus motif for PI(3,4,5)P3-interacting pleckstrin homology (PH) domains, which enabled in silico identification of phosphoinositide interactors. Members of the dedicator of cytokinesis family C exhibited specificity toward both PI(3,4,5)P3 and PI(4,5)P2. Structurally, this dual specificity is explained by a decreased number of positively charged residues in the L1 subdomain compared with DOCK1. The presented PIP-binding proteome and its specificity toward individual PIPs should be a valuable resource for the community.http://www.sciencedirect.com/science/article/pii/S2211124713007961 |
| spellingShingle | Stephanie Jungmichel Kathrine B. Sylvestersen Chunaram Choudhary Steve Nguyen Matthias Mann Michael L. Nielsen Specificity and Commonality of the Phosphoinositide-Binding Proteome Analyzed by Quantitative Mass Spectrometry Cell Reports |
| title | Specificity and Commonality of the Phosphoinositide-Binding Proteome Analyzed by Quantitative Mass Spectrometry |
| title_full | Specificity and Commonality of the Phosphoinositide-Binding Proteome Analyzed by Quantitative Mass Spectrometry |
| title_fullStr | Specificity and Commonality of the Phosphoinositide-Binding Proteome Analyzed by Quantitative Mass Spectrometry |
| title_full_unstemmed | Specificity and Commonality of the Phosphoinositide-Binding Proteome Analyzed by Quantitative Mass Spectrometry |
| title_short | Specificity and Commonality of the Phosphoinositide-Binding Proteome Analyzed by Quantitative Mass Spectrometry |
| title_sort | specificity and commonality of the phosphoinositide binding proteome analyzed by quantitative mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713007961 |
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