PXD022297

PXD022297 is an original dataset announced via ProteomeXchange.

Title	Dynamic 3D proteomes reveal functional pathway alterations in situ
Description	Many biological processes are regulated via molecular events, such as intermolecular interactions and chemical modifications, which do not affect protein levels and escape detection in classical proteomic screens. Reasoning that these events affect protein structure, we propose here that a global protein structural readout could detect many functional alterations simultaneously and in situ. We test this idea using limited proteolysis-mass spectrometry (LiP-MS), which monitors structural changes in thousands of proteins within a native-like environment. In bacteria undergoing nutrient adaptation and in yeast responding to acute stress, this global structural readout captures enzyme activity changes, allosteric regulation, phosphorylation, protein aggregation and protein complex formation, with sufficiently high resolution to identify alterations of single functional sites such as active site occupancy and binding interfaces. Comparison with prior knowledge, including flux, phosphoproteomics and metabolomics data, shows that LiP-MS captures most known enzyme functional alterations and suggests novel metabolite-protein binding events, enabling identification of a fructose-1,6-bisphosphate-based regulatory mechanism of glucose uptake in E. coli. The structural readout dramatically increases classical proteomics screen coverage and generates mechanistic hypotheses, thus better linking holistic and reductionist approaches and paving the way for a new in situ structural systems biology.
HostingRepository	PRIDE
AnnounceDate	2022-02-14
AnnouncementXML	Submission_2022-02-13_16:44:28.290.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ludovic Gillet
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-02 03:36:26	ID requested
1	2020-11-02 07:49:22	announced
2	2021-01-04 04:00:04	announced	2021-01-04: Updated publication reference for PubMed record(s): 33357446.
⏵ 3	2022-02-13 16:44:29	announced	2022-02-14: Updated project metadata.

Cappelletti V, Hauser T, Piazza I, Pepelnjak M, Malinovska L, Fuhrer T, Li Y, D, ö, rig C, Boersema P, Gillet L, Grossbach J, Dugourd A, Saez-Rodriguez J, Beyer A, Zamboni N, Caflisch A, de Souza N, Picotti P, Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ. Cell, 184(2):545-559.e22(2021) [pubmed]

ProteomeXchange project tag: EPIC-XS

submitter keyword: LC-MSMS, Heat shock, Metabolism, DIA, limited proteolysis, structural barcodes, Osmotic stress, DDA,Structure-function, Shotgun proteomics

Paola Picotti
contact affiliation	Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland
contact email	picotti@imsb.biol.ethz.ch
lab head
Ludovic Gillet
contact affiliation	ETH Zurich
contact email	gillet@imsb.biol.ethz.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/11/PXD022297

PRIDE project URI

• PRIDE
  1. PXD022297
     1. Label: PRIDE project
     2. Name: Dynamic 3D proteomes reveal functional pathway alterations in situ