کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2041877 | 1073176 | 2014 | 14 صفحه PDF | دانلود رایگان |
• The PIP-binding interactome was characterized by quantitative proteomics
• A total of 405 phosphoinositide-binding proteins were identified
• Translocation and inhibitor assays confirm identified targets as direct interactors
• The PIP-binding proteome encompasses proteins from diverse cellular compartments
SummaryPhosphoinositides (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.
Graphical AbstractFigure optionsDownload as PowerPoint slide
Journal: - Volume 6, Issue 3, 13 February 2014, Pages 578–591