Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ
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Date
2021-01-21
Publication Type
Journal Article
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yes
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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.
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published
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Journal / series
Volume
184 (2)
Pages / Article No.
545 - 5.59e+24
Publisher
Cell Press
Event
Edition / version
Methods
Software
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Date collected
Date created
Subject
structural proteomics; mass spectrometry; limited proteolysis; structural systems biology; protein aggregation; functional proteomics; metabolism; structural biology; yeast; E. coli
Organisational unit
03927 - Picotti, Paola / Picotti, Paola
08839 - Zamboni, Nicola (Tit.-Prof.)
Notes
Funding
866004 - Three-dimensional dynamic views of proteomes as a novel readout for physiolgical and pathological alterations (EC)
823839 - European Proteomics Infrastructure Consortium providing Access (EC)
177195 - Molecular and Cellular Modulation in Parkinson's Disease (SNF)
823839 - European Proteomics Infrastructure Consortium providing Access (EC)
177195 - Molecular and Cellular Modulation in Parkinson's Disease (SNF)