PXD038239-1

PXD038239 is an original dataset announced via ProteomeXchange.

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	2023-09-06
AnnouncementXML	Submission_2023-09-06_09:49:10.461.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	HaoxinLi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-21 16:15:43	ID requested
⏵ 1	2023-09-06 09:49:10	announced
2	2023-11-14 07:54:33	announced	2023-11-14: Updated project metadata.

submitter keyword: cysteine,Base editing, electrophile, cancer dependency, ligandability

BenjaminCravatt
contact affiliation	Department of Chemistry, Scripps Research, La Jolla, CA 92037 USA
contact email	cravatt@scripps.edu
lab head
HaoxinLi
contact affiliation	The Scripps Research Institute
contact email	haoxinli@scripps.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038239
     1. Label: PRIDE project
     2. Name: Assigning functionality to cysteines by base editing of cancer dependency genes