PXD031393

PXD031393 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 various aspects of cellular behavior 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 activation is limited, 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	PanoramaPublic
AnnounceDate	2024-03-31
AnnouncementXML	Submission_2024-03-31_20:35:56.674.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Ruth Huttenhain
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl
Instrument	TSQ Quantiva

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-01 15:22:55	ID requested
⏵ 1	2024-03-31 20:35:57	announced

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, 20(9):1133-1143(2024) [pubmed]

submitter keyword: SRM, APEX, proximity labeling, GPCR, mu-opioid receptor

Ruth Huttenhain
contact affiliation	Department of Cellular and Molecular Pharmacology
contact email	ruthh@stanford.edu
lab head
Ruth Huttenhain
contact affiliation	Department of Cellular and Molecular Pharmacology
contact email	ruthh@stanford.edu
dataset submitter

Panorama Public dataset URI