PXD049322-1

PXD049322 is an original dataset announced via ProteomeXchange.

Title	An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells
Description	Electrophilic compounds originating from nature or chemical synthesis have profound effects on immune cells. These compounds are thought to act by cysteine modification to alter the functions of immune-relevant proteins; however, our understanding of electrophile-sensitive cysteines in the human immune proteome remains limited. Here, we present a global map of cysteines in primary human T cells that are susceptible to covalent modification by electrophilic small molecules. More than 3,000 covalently liganded cysteines were found on functionally and structurally diverse proteins, including many that play fundamental roles in immunology. We further show that electrophilic compounds can impair T cell activation by distinct mechanisms involving the direct functional perturbation and/or degradation of proteins. Our findings reveal a rich content of ligandable cysteines in human T cells and point to electrophilic small molecules as a fertile source for chemical probes and ultimately therapeutics that modulate immunological processes and their associated disorders.
HostingRepository	PRIDE
AnnounceDate	2024-02-12
AnnouncementXML	Submission_2024-02-12_10:08:33.674.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ekaterina Vinogradova
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-11 17:41:06	ID requested
⏵ 1	2024-02-12 10:08:34	announced

Vinogradova EV, Zhang X, Remillard D, Lazar DC, Suciu RM, Wang Y, Bianco G, Yamashita Y, Crowley VM, Schafroth MA, Yokoyama M, Konrad DB, Lum KM, Simon GM, Kemper EK, Lazear MR, Yin S, Blewett MM, Dix MM, Nguyen N, Shokhirev MN, Chin EN, Lairson LL, Melillo B, Schreiber SL, Forli S, Teijaro JR, Cravatt BF, An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell, 182(4):1009-1026.e29(2020) [pubmed]

10.1016/j.cell.2020.07.001;

submitter keyword: cysteine,activity-based protein profiling, BIRC3, chemical proteomics, covalent electrophiles, protein degradation, human T cells, ITK

Benjamin F. Cravatt
contact affiliation	Department of Chemistry, The Scripps Research Institute
contact email	cravatt@scripps.edu
lab head
Ekaterina Vinogradova
contact affiliation	The Rockefeller University
contact email	vinograd@rockefeller.edu
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/2024/02/PXD049322

PRIDE project URI

• PRIDE
  1. PXD049322
     1. Label: PRIDE project
     2. Name: An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells