PXD042403

PXD042403 is an original dataset announced via ProteomeXchange.

Title	Stratifying the Cell Surface Cysteinome using Two-step Enrichment Proteomics
Description	Cell surface cysteines represent an attractive class of residues for chemoproteomic studies due to their accessibility towards drugs and key roles they play in the structure and function of most human proteins. The redox sensitivity of cysteines also makes cell surface cysteines potential markers for cellular activities with altered redox states. However, cell surface cysteines are underrepresented in most of the cysteine proteomic dataset. While many mass spectrometry (MS) based techniques have been developed to enrich membrane proteins, current studies lack methods that can specifically inventory cysteines on cell surfaces. Here, we developed a novel dual enrichment method to achieve chemoproteomic profiling of cell Surface Cysteines - “Cys-Surf''. Combining cell surface capture (CSC) biotinylation and cysteine chemoproteomic biotinylation, this two-step biotinylation platform achieves identification of more than 1,900 cysteines with a specificity of about 50.0% in cell surface localization. In addition, Cys-Surf achieved quantitative analysis of oxidation states of cell surface cysteines, which reflect a completely different profile compared to that of the whole cysteinome. Redox sensitive cell surface cysteines were identified by applying reducing reagents and during T cell activation. Cys-Surf is also compatible with competitive small-molecule screening by isotopic tandem orthogonal activity-based protein profiling (isoTOP-ABPP) to evaluate the ligandability of cell surface cysteines. Altogether, these findings establish a platform that enables redox and ligandability analysis of the cell surface cysteinome and sheds light on future functional studies and drug discovery efforts targeting cell surface cysteines.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_10:22:31.803.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tianyang Yan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-22 10:11:33	ID requested
⏵ 1	2024-01-26 10:22:32	announced

Yan T, Boatner LM, Cui L, Tontonoz PJ, Backus KM, Defining the Cell Surface Cysteinome Using Two-Step Enrichment Proteomics. JACS Au, 3(12):3506-3523(2023) [pubmed]

10.1021/jacsau.3c00707;

submitter keyword: Oxidation states, T cell activation, Cysteines, Chemoproteomics,Cell surface

Keriann Backus
contact affiliation	Department of Biological Chemistry, UCLA
contact email	KBackus@mednet.ucla.edu
lab head
Tianyang Yan
contact affiliation	Department of Chemistry and Biochemistry, UCLA
contact email	tyyan14@outlook.com
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/2024/01/PXD042403

PRIDE project URI

• PRIDE
  1. PXD042403
     1. Label: PRIDE project
     2. Name: Stratifying the Cell Surface Cysteinome using Two-step Enrichment Proteomics