PXD049391

PXD049391 is an original dataset announced via ProteomeXchange.

Title	Molecular mechanism of β-arrestin-2 pre-activation by phosphatidylinositol 4,5-bisphosphate
Description	Arrestins are a protein family that regulate G protein-coupled receptor (GPCR) signaling, with four distinct members in mammals (arrestin 1–4). Phosphorylated residues of G protein-coupled receptors bind to the N-domain of arrestin, resulting in C-terminus release. This induces further allosteric conformational changes, such as polar core disruption, alteration of interdomain loops, and domain rotation, which transform arrestins into the receptor-activated state. It is widely accepted that arrestin activation occurs by conformational changes propagated from the N- to the C-domain. However, recent studies have revealed that binding of phosphatidylinositol 4,5-bisphosphate (PIP2) to the C-domain transforms arrestins into an active state. In this study, we aimed to elucidate the mechanisms underlying PIP2-induced arrestin activation. We compared the conformational changes of β-arrestin-2 upon binding of PIP2 or phosphorylated C-tail peptide of vasopressin receptor type 2 (V2Rpp) using hydrogen/deuterium exchange mass spectrometry (HDX-MS). Introducing point mutations on the potential routes of the allosteric conformational changes and analyzing these mutant constructs with HDX-MS revealed that PIP2-binding at the C-domain affects the back loop, which destabilizes the gate loop and β-strand XX to transform β-arrestin-2 into the pre-active state.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:49:49.856.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kiae Kim
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Xevo G2 Q-Tof

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-14 16:32:37	ID requested
1	2024-07-15 01:53:14	announced
⏵ 2	2024-10-22 06:49:50	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Arrestin,Hydrogen/deuterium exchange mass spectrometry (HDX-MS),5-bisphosphate, phosphatidylinositol 4

Ka Young
contact affiliation	School of Pharmacy, Sungkyunkwan University, South Korea
contact email	kychung2@skku.edu
lab head
Kiae Kim
contact affiliation	Sungkyunkwan University
contact email	kimkiae95@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/2024/07/PXD049391

PRIDE project URI

• PRIDE
  1. PXD049391
     1. Label: PRIDE project
     2. Name: Molecular mechanism of β-arrestin-2 pre-activation by phosphatidylinositol 4,5-bisphosphate