PXD031415

PXD031415 is an original dataset announced via ProteomeXchange.

Title	Profiling the diversity of agonist-selective effects on the proximal proteome environment of G protein-coupled receptors
Description	G protein-coupled receptors (GPCRs) regulate many aspects of physiology and represent actionable targets for drug discovery. Activation of specific signaling pathways downstream of G-protein coupled receptors (GPCRs) or targeting the receptors at selected cellular locations has the potential to provide therapeutic actions with fewer side effects. However, the understanding of the molecular mechanisms underlying GPCR function is limited in the dynamic cellular environment, hampering drug discovery efforts towards selective ligands. Proximity biotin labeling based on an engineered ascorbic acid peroxidase (APEX) combined with quantitative mass spectrometry is a powerful method to delineate these mechanisms given its capacity to simultaneously capture proximal protein interaction networks and the cellular location of the receptor. However, a major challenge is to extract the various information from these complex datasets. Here, we describe a computational framework for proximity labeling datasets which predicts ligand-dependent subcellular location of GPCRs and quantitatively deconvolutes the effect of receptor location and proximal interactors. We applied this approach to the mu-opioid receptor and not only monitored distinct effects of ligands on receptor trafficking, but also discovered two novel regulators, EYA4 and KCTD12, which modulate MOR-driven G protein-dependent signaling.
HostingRepository	PRIDE
AnnounceDate	2024-03-30
AnnouncementXML	Submission_2024-03-30_03:52:45.641.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ruth Huttenhain
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Q Exactive; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-03 08:15:09	ID requested
⏵ 1	2024-03-30 03:52:46	announced

10.1038/s41589-024-01588-3;

Polacco BJ, Lobingier BT, Blythe EE, Abreu N, Khare P, Howard MK, Gonzalez-Hernandez AJ, Xu J, Li Q, Novy B, Naing ZZC, Shoichet BK, Coyote-Maestas W, Levitz J, Krogan NJ, Von Zastrow M, H, ü, ttenhain R, -opioid receptor. Nat Chem Biol, ():(2024) [pubmed]

submitter keyword: AP-MS, mu opioid receptor, DIA,APEX, GPCR, DDA

Ruth Huttenhain
contact affiliation	Department of Cellular and Molecular Pharmamcology, UCSF
contact email	ruth.huttenhain@ucsf.edu
lab head
Ruth Huttenhain
contact affiliation	UCSF
contact email	ruth.huttenhain@ucsf.edu
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/2024/03/PXD031415

PRIDE project URI

• PRIDE
  1. PXD031415
     1. Label: PRIDE project
     2. Name: Profiling the diversity of agonist-selective effects on the proximal proteome environment of G protein-coupled receptors