PXD056863

PXD056863 is an original dataset announced via ProteomeXchange.

Title	Engineering CRBN for high throughput screening and molecular glue discovery
Description	The majority of clinical degraders utilize an immunomodulatory imide drug (IMiD)-based derivative, that directs their target to the E3 ligase receptor Cereblon (CRBN), however, identification of new IMiD molecular glue substrates has remained underexplored. To tackle this, we design human CRBN constructs which retain all features for ternary complex formation, whilst allowing generation of homogenous and cost-efficient expression in E.coli. Extensive profiling of the construct, shows it to be the “best of both worlds” in terms of binding activity and ease of production. We next designed the ‘Enamine focused IMiD library’ and demonstrated applicability of the construct to high-throughput screening, identifying novel binders with high potency, ligand efficiency and specificity. Finally, we adapt our construct for proof of principle glue screening approaches enabling IMiD cellular interactome determination. Coupled with our IMiD binding landscape the methods described here should serve as valuable tools to assist discovery of next generation CRBN glues
HostingRepository	PRIDE
AnnounceDate	2024-12-06
AnnouncementXML	Submission_2024-12-06_03:06:28.721.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rubina Kazi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-16 10:17:29	ID requested
⏵ 1	2024-12-06 03:06:29	announced

Bailey HJ, Eisert J, Kazi R, Gerhartz J, Pie, ń, kowska DE, Dressel I, Vollrath J, Kondratov I, Matviyuk T, Tolmachova N, Shah VJ, Giuliani G, Mosler T, Geiger TM, Esteves AM, Santos SP, Sousa RL, Bandeiras TM, Leibrock EM, Bauer U, Leuthner B, Langer JD, Wegener AA, Nowak RP, Sorrell FJ, Dikic I, An engineered cereblon optimized for high throughput screening and molecular glue discovery. Cell Chem Biol, ():(2024) [pubmed]

10.1016/j.chembiol.2024.11.002;

submitter keyword: CoIP,FlagCRBN, WCP

Ivan Dikic
contact affiliation	Professor of Biochemistry Director,Institute of Biochemistry II, Group leader, Buchmann Institute for Molecular Life Sciences University Hospital of Goethe University Frankfurt
contact email	dikic@biochem2.uni-frankfurt.de
lab head
Rubina Kazi
contact affiliation	Postdoc
contact email	kazi@med.uni-frankfurt.de
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/2024/12/PXD056863

PRIDE project URI

• PRIDE
  1. PXD056863
     1. Label: PRIDE project
     2. Name: Engineering CRBN for high throughput screening and molecular glue discovery