PXD043348

PXD043348 is an original dataset announced via ProteomeXchange.

Title	A chemical probe unravels the reactive proteome of health-associated catechols
Description	Catechol-containing natural products are common constituents of foods, drinks, and drugs. Natural products carrying this motif are often associated with beneficial biological effects such as anticancer activity and neuroprotection. However, the molecular mode of action behind these properties is poorly understood. Here, we apply a mass spectrometry-based competitive chemical proteomics approach to elucidate the target scope of catechol-containing bioactive molecules from diverse foods and drugs. Inspired by the protein reactivity of catecholamine neurotransmitters, we designed and synthesised a broadly reactive minimalist catechol chemical probe based on dopamine. Initial labelling experiments in live human cells demonstrated broad protein binding by the probe, which was largely outcompeted by its parent compound dopamine. Next, we investigated the competition profile of a selection of biologically relevant catechol-containing compounds. With this approach, we characterised the protein reactivity and the target scope of dopamine and ten catechols. Strikingly, proteins associated with the endoplasmic reticulum (ER) were among the main targets. ER stress assays in the presence of reactive catechols revealed an activation of the IRE1-branch of the unfolded protein response (UPR), whereas unreactive catechols had no effect. As the UPR is an intriguing oncology target, this provides a possible explanation of the health-promoting effects attributed to many catechol natural products.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:12:35.969.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Angela Weigert Muñoz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-27 11:27:01	ID requested
1	2023-10-24 14:33:18	announced
⏵ 2	2023-11-14 09:12:36	announced	2023-11-14: Updated project metadata.

Weigert Mu, ñ, oz A, Meighen-Berger KM, Hacker SM, Feige MJ, Sieber SA, A chemical probe unravels the reactive proteome of health-associated catechols. Chem Sci, 14(32):8635-8643(2023) [pubmed]

submitter keyword: dopamine, catechols, Q Exactive Plus, SH-SY5Y,human, HEK293, LC-MS/MS

Stephan A. Sieber
contact affiliation	Center for Functional Protein Assemblies, Technical University of Germany, Germany
contact email	stephan.sieber@tum.de
lab head
Angela Weigert Muñoz
contact affiliation	Center for functional protein assemblies, Technical University of Munich, Ernst-Otto-Fischer-Straße 8, D-85748 Garching
contact email	angela.weigert-munoz@tum.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/2023/10/PXD043348

PRIDE project URI

• PRIDE
  1. PXD043348
     1. Label: PRIDE project
     2. Name: A chemical probe unravels the reactive proteome of health-associated catechols