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PXD049391-2

PXD049391 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMolecular mechanism of β-arrestin-2 pre-activation by phosphatidylinositol 4,5-bisphosphate
DescriptionArrestins 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:49:49.856.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKiae Kim
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationListNo PTMs are included in the dataset
InstrumentXevo G2 Q-Tof
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-14 16:32:37ID requested
12024-07-15 01:53:14announced
22024-10-22 06:49:50announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Arrestin,Hydrogen/deuterium exchange mass spectrometry (HDX-MS),5-bisphosphate, phosphatidylinositol 4
Contact List
Ka Young
contact affiliationSchool of Pharmacy, Sungkyunkwan University, South Korea
contact emailkychung2@skku.edu
lab head
Kiae Kim
contact affiliationSungkyunkwan University
contact emailkimkiae95@skku.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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