PXD061425-1

PXD061425 is an original dataset announced via ProteomeXchange.

Title	Structure-guided development of chemically tailored peptide binders of RNF43/ZNRF3 to enable versatile design of membrane protein-targeting PROTACs
Description	Targeted membrane protein degradation using cell surface E3 ligases RNF43/ZNRF3 via proteolysis targeting chimeras (PROTACs) represents an effective strategy for treating membrane drug targets that cannot be fully inhibited using traditional inhibitors. Several ingenious chimeras have been developed to tether RNF43/ZNRF3 to target membrane proteins, resulting in the degradation of targets at sub-nanomolar concentrations both in vitro and in vivo. However, currently available RNF43/ZNRF3 binders are genetically encoded and have poor plasticity, which limits the design and promotion of such PROTACs. Here, we exploited the AlphaFold-predicted complex structures of ligand-bound RNF43/ZNRF3 and developed a class of chemically tailored peptide binders for ZNRF3/RNF43. With these peptide binders that can be conveniently prepared by de novo peptide synthesis, we established a new membrane protein degradation platform that allows versatile modular design and targeted degradation of clinically relevant membrane proteins, i.e. PD-L1 and EGFR. This study presents a new subtype within the PROTAC field to develop therapeutic peptides targeting membrane proteins.
HostingRepository	iProX
AnnounceDate	2025-03-04
AnnouncementXML	Submission_2025-03-03_19:34:22.306.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yicheng Weng
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue; methionine oxidation with neutral loss of 64 Da
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-03 19:34:06	ID requested
⏵ 1	2025-03-03 19:34:23	announced

Cui J, Zheng Q, Weng Y, Zhai X, Su Z, Du Y, Wei X, Yu Y, Qu Q, Pan M, Structure-Guided Development of Chemically Tailored Peptide Binders of RNF43/ZNRF3 to Enable Versatile Design of Membrane Protein-Targeting PROTACs. Angew Chem Int Ed Engl, 64(19):e202501488(2025) [pubmed]

submitter keyword: PROTAC, RSPO, PDL1

Man Pan
contact affiliation	Shanghai Jiao Tong University
contact email	panman@sjtu.edu.cn
lab head
Yicheng Weng
contact affiliation	Shanghai Jiao Tong University
contact email	wengyc12@qq.com
dataset submitter

iProX dataset URI