PXD038232 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Assigning functionality to cysteines by base editing of cancer dependency genes |
Description | Chemical probes are lacking for most human proteins. Covalent chemistry represents an attractive strategy for expanding the ligandability of the proteome, and chemical proteomics has revealed numerous electrophile-reactive cysteines on diverse proteins. Determining which of these covalent binding events impact protein function, however, remains challenging. Here, we describe a base-editing strategy to infer the functionality of cysteines by quantifying the impact of their missense mutation on cell proliferation. We show that the resulting atlas, which covers >13,800 cysteines on >1,750 cancer dependency proteins, correctly predicts the essentiality of cysteines targeted by cancer therapeutics and, when integrated with chemical proteomic data, identifies essential, ligandable cysteines on >110 cancer dependency proteins. We finally demonstrate how measurements of reactivity in native versus denatured proteomes can further discriminate essential cysteines amendable to chemical modification from those buried in protein structures, providing a valuable resource to prioritize the pursuit of small-molecule probes with high function-perturbing potential. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_07:58:31.967.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Haoxin Li |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-11-21 15:51:07 | ID requested | |
1 | 2023-09-06 10:22:53 | announced | |
⏵ 2 | 2023-11-14 07:58:32 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: cysteine,Base editing, electrophile, cancer dependency, ligandability |
Contact List
Benjamin Cravatt |
contact affiliation | Department of Chemistry, Scripps Research, La Jolla, CA 92037 USA |
contact email | cravatt@scripps.edu |
lab head | |
Haoxin Li |
contact affiliation | The Scripps Research Institute |
contact email | haoxinli@scripps.edu |
dataset submitter | |
Full Dataset Link List
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/2023/09/PXD038232 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD038232
- Label: PRIDE project
- Name: Assigning functionality to cysteines by base editing of cancer dependency genes