PXD042888

PXD042888 is an original dataset announced via ProteomeXchange.

Title	A Chemical Proteomics Approach for Global Mapping of Functional Lysines on Cell Surface of Living Cell
Description	Cell surface proteins are responsible for many crucial physiological roles, and they are also the major category of drug targets as the majority of therapeutics target membrane proteins on the surface of cells to alter cellular signaling. How-ever, despite its great significance, ligand discovery against membrane proteins has posed a great challenge mainly due to the special property of their natural habitat. Here, we design a new chemical proteomic probe OPA-S-S-alkyne that can efficiently and selectively target the lysine exposed on the cell surface and develop a chemical proteomics strategy for global analysis of surface functionality (GASF) in living cells. In total, we quantified 2639 cell surface lysines with >90% specificity in Hela cell and several hundred residues with heightened reactivity were discovered, which represents the largest dataset of surface functional lysine sites to date. We discovered and validated that hyper-reactive lysine residues K382 on tyrosine kinase-like orphan receptor 2 (ROR2) and K285 on Endoglin (ENG/CD105) are at the protein interac-tion interface in co-crystal structures of protein complexes, emphasizing the broad potential functional consequences of cell surface lysines and GASF strategy is highly desirable for discovering new active and ligandable sites that can be func-tionally interrogated for drug discovery.
HostingRepository	iProX
AnnounceDate	2024-03-01
AnnouncementXML	Submission_2024-10-11_23:59:05.829.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shiyun Ma
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue; (13)C labeled residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-11 20:09:32	ID requested
⏵ 1	2024-10-11 23:59:10	announced

Wang T, Ma S, Ji G, Wang G, Liu Y, Zhang L, Zhang Y, Lu H, A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun, 15(1):2997(2024) [pubmed]

submitter keyword: ABPP, cell surface, lysine reactivity, chemical proteomics, living cell labeling

Haojie Lu
contact affiliation	Fudan University
contact email	luhaojie@fudan.edu.cn
lab head
Shiyun Ma
contact affiliation	Fudan University
contact email	22110220054@m.fudan.edu.cn
dataset submitter

iProX dataset URI