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

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)...

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Main Authors: Cappelletti, Valentina (Author) , Hauser, Thomas (Author) , Piazza, Ilaria (Author) , Pepelnjak, Monika (Author) , Malinovska, Liliana (Author) , Fuhrer, Tobias (Author) , Li, Yaozong (Author) , Dörig, Christian (Author) , Boersema, Paul (Author) , Gillet, Ludovic (Author) , Grossbach, Jan (Author) , Dugourd, Aurélien (Author) , Sáez Rodríguez, Julio (Author) , Beyer, Andreas (Author) , Zamboni, Nicola (Author) , Caflisch, Amedeo (Author) , de Souza, Natalie (Author) , Picotti, Paola (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Cell
Year: 2021, Volume: 184, Issue: 2, Pages: 545-559
ISSN:1097-4172
DOI:10.1016/j.cell.2020.12.021
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cell.2020.12.021
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867420316913
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Author Notes:Valentina Cappelletti, Thomas Hauser, Ilaria Piazza, Monika Pepelnjak, Liliana Malinovska, Tobias Fuhrer, Yaozong Li, Christian Dörig, Paul Boersema, Ludovic Gillet, Jan Grossbach, Aurelien Dugourd, Julio Saez-Rodriguez, Andreas Beyer, Nicola Zamboni, Amedeo Caflisch, Natalie de Souza, and Paola Picotti
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Summary: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.
Item Description:Das PDF enthält zusätzlich einen Anhang von 13 Seiten
Available online 23 December 2020
Gesehen am 08.09.2021
Physical Description:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2020.12.021

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