PXD041225-1

PXD041225 is an original dataset announced via ProteomeXchange.

Title	Targeted protein degradation using E2 ubiquitin-conjugating enzymes
Description	Proteins can be targeted for degradation by using engineered molecular conjugates to enhance their interaction with eukaryotic ubiquitination machinery. For instance, the fusion of an E3 ubiquitin ligase to a suitable target binding domain creates a biological ‘Proteolysis-Targeting Chimera’ (bioPROTAC). Here we report an analogous approach where the target is recruited directly to an E2 ubiquitin-conjugating enzyme via an attached target binding domain. We demonstrate that E2 bioPROTACs can induce the degradation of the human proteins SHP2, KRAS and Human Antigen R (HuR). Taking advantage of both rational and unbiased combinatorial screening, we identified novel SHP2 degraders that possess unusually weak affinity. Finally, we explored the proteomic impact of E2 vs. E3 bioPROTACs to inform on their wider impact on the cellular proteome.
HostingRepository	PRIDE
AnnounceDate	2024-09-23
AnnouncementXML	Submission_2024-09-23_04:33:44.471.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fiona Pachl
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-30 12:57:18	ID requested
⏵ 1	2024-09-23 04:33:45	announced
2	2024-10-22 06:59:19	announced	2024-10-22: Updated project metadata.

10.1038/s42003-024-06803-4;

Taylor JD, Barrett N, Martinez Cuesta S, Cassidy K, Pachl F, Dodgson J, Patel R, Eriksson TM, Riley A, Burrell M, Bauer C, Rees DG, Cimbro R, Zhang AX, Minter RR, Hunt J, Legg S, Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes. Commun Biol, 7(1):1179(2024) [pubmed]

submitter keyword: bioPROTAC

Andrew Zhang
contact affiliation	Discovery Biology, AstraZeneca Pharmaceuticals
contact email	andrewzhang@astrazeneca.com
lab head
Fiona Pachl
contact affiliation	AstraZeneca
contact email	fiona.pachl@astrazeneca.com
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/2024/09/PXD041225

PRIDE project URI

• PRIDE
  1. PXD041225
     1. Label: PRIDE project
     2. Name: Targeted protein degradation using E2 ubiquitin-conjugating enzymes