PXD049391 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD049391
- Label: PRIDE project
- Name: Molecular mechanism of β-arrestin-2 pre-activation by phosphatidylinositol 4,5-bisphosphate