PXD065019

PXD065019 is an original dataset announced via ProteomeXchange.

Title	The interactions between β-Arrestin 1 and Gαs or Gαi1: functional and structural insights
Description	G proteins and arrestins are key G protein-coupled receptor (GPCR) signaling transducers, mediating distinct downstream pathways. Recent evidence suggests that G proteins and β-arrestins (βarrs) can directly or functionally interact through GPCR–G protein–βarr megaplexes, direct βarr1–Gαs interactions, and Gαi–βarr complexes that regulate ERK activation. However, the molecular details and functional consequences of βarr–Gα interactions remain poorly understood. Here, we quantified the binding affinities between βarr1 and Gαs or Gαi1 in various activation states using microscale thermophoresis (MST). βarr1 active state favored binding, whereas Gα activation state was less determinant. To assess functional outcomes, we employed a BODIPY-FL–GTPγS assay for Gα activation and a βarr1 β-strand XX (βXX) release assay for arrestin activation. βarr1 did not affect GDP/GTP turnover of Gα; however, Gαs enhanced V2Rpp-induced βarr1 activation. Hydrogen/deuterium exchange mass spectrometry revealed conformational changes in both the Ras-like and α-helical domains of Gα subunits upon βarr1 binding, and localized changes in the βarr1 lariat loop. These findings define domain-level interfaces and support a cooperative mechanism by which Gαs facilitates GPCR-driven βarr1 activation.
HostingRepository	PRIDE
AnnounceDate	2026-02-24
AnnouncementXML	Submission_2026-02-24_04:02:49.012.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Longhan Duan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q-Tof Ultima

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-14 08:53:03	ID requested
⏵ 1	2026-02-24 04:02:49	announced

10.1038/s41467-026-68690-z;

Duan L, Kim H, Suh Y, Ahn D, Kim S, Hyun J, Kwon Y, Seong J, Chung KY, i1. Nat Commun, 17(1):(2026) [pubmed]

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: G protein, Protein–protein interaction,AArrestin, GPCR signaling

Longhan Duan, Ka Young Chung
contact affiliation	School of Pharmacy, Sungkyunkwan University, South Korea
contact email	kychung2@skku.edu
lab head
Longhan Duan
contact affiliation	School of Pharmacy, Sungkyunkwan University, South Korea
contact email	noraline@skku.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/2026/02/PXD065019

PRIDE project URI

• PRIDE
  1. PXD065019
     1. Label: PRIDE project
     2. Name: The interactions between β-Arrestin 1 and Gαs or Gαi1: functional and structural insights