Cappelletti, Valentina, Hauser, Thomas, Piazza, Ilaria ORCID: 0000-0001-5895-6134, Pepelnjak, Monika, Malinovska, Liliana ORCID: 0000-0002-8514-4569, Fuhrer, Tobias, Li, Yaozong ORCID: 0000-0002-5796-2644, Doerig, Christian, Boersema, Paul, Gillet, Ludovic, Grossbach, Jan, Dugourd, Aurelien, Saez-Rodriguez, Julio ORCID: 0000-0002-8552-8976, Beyer, Andreas ORCID: 0000-0002-3891-2123, Zamboni, Nicola ORCID: 0000-0003-1271-1021, Caflisch, Amedeo, de Souza, Natalie and Picotti, Paola ORCID: 0000-0002-4109-3552 (2021). Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ. Cell, 184 (2). S. 545 - 582. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Cappelletti, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauser, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piazza, IlariaUNSPECIFIEDorcid.org/0000-0001-5895-6134UNSPECIFIED
Pepelnjak, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malinovska, LilianaUNSPECIFIEDorcid.org/0000-0002-8514-4569UNSPECIFIED
Fuhrer, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, YaozongUNSPECIFIEDorcid.org/0000-0002-5796-2644UNSPECIFIED
Doerig, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boersema, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gillet, LudovicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grossbach, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dugourd, AurelienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saez-Rodriguez, JulioUNSPECIFIEDorcid.org/0000-0002-8552-8976UNSPECIFIED
Beyer, AndreasUNSPECIFIEDorcid.org/0000-0002-3891-2123UNSPECIFIED
Zamboni, NicolaUNSPECIFIEDorcid.org/0000-0003-1271-1021UNSPECIFIED
Caflisch, AmedeoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Souza, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Picotti, PaolaUNSPECIFIEDorcid.org/0000-0002-4109-3552UNSPECIFIED
URN: urn:nbn:de:hbz:38-592537
DOI: 10.1016/j.cell.2020.12.021
Journal or Publication Title: Cell
Volume: 184
Number: 2
Page Range: S. 545 - 582
Date: 2021
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ENZYME-I; MOLECULAR-DYNAMICS; ESCHERICHIA-COLI; HIGH-THROUGHPUT; HEAT-SHOCK; ALLOSTERIC REGULATION; SOMATIC MUTATIONS; FORCE-FIELD; YEAST; COMPLEXMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59253

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