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Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ

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Item Type:Article
Title:Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ
Creators Name:Cappelletti, V. and Hauser, T. and Piazza, I. and Pepelnjak, M. and Malinovska, L. and Fuhrer, T. and Li, Y. and Dörig, C. and Boersema, P. and Gillet, L. and Grossbach, J. and Dugourd, A. and Saez-Rodriguez, J. and Beyer, A. and Zamboni, N. and Caflisch, A. and de Souza, N. and Picotti, P.
Abstract:Biological processes are regulated by intermolecular interactions and chemical modifications that do not affect protein levels, thus escaping detection in classical proteomic screens. We demonstrate here that a global protein structural readout based on limited proteolysis-mass spectrometry (LiP-MS) detects many such functional alterations, simultaneously and in situ, in bacteria undergoing nutrient adaptation and in yeast responding to acute stress. The structural readout, visualized as structural barcodes, captured enzyme activity changes, phosphorylation, protein aggregation, and complex formation, with the resolution of individual regulated functional sites such as binding and active sites. Comparison with prior knowledge, including other 'omics data, showed that LiP-MS detects many known functional alterations within well-studied pathways. It suggested distinct metabolite-protein interactions and enabled identification of a fructose-1,6-bisphosphate-based regulatory mechanism of glucose uptake in E. coli. The structural readout dramatically increases classical proteomics coverage, generates mechanistic hypotheses, and paves the way for in situ structural systems biology.
Keywords:Structural Proteomics, Mass Spectrometry, Limited Proteolysis, Structural Systems Biology, Protein Aggregation, Functional Proteomics, Metabolism, Structural Biology, Yeast, E. coli
Source:Cell
ISSN:0092-8674
Publisher:Cell Press
Volume:184
Number:2
Page Range:545-559
Date:21 January 2021
Official Publication:https://doi.org/10.1016/j.cell.2020.12.021
PubMed:View item in PubMed

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