PXD012894

PXD012894 is an original dataset announced via ProteomeXchange.

Title	Selective Binding of a Toxin and Phosphatidylinositides to a Mammalian Potassium Channel
Description	G-protein-gated inward rectifying potassium channels (GIRKs) require Gβγ subunits and phosphorylated phosphatidylinositides (PIPs) for gating. Although studies have provided insight into these interactions, the mechanism of how these events are modulated by Gβγ and the binding affinity between PIPs and GIRKs remains poorly understood. Here, native ion mobility mass spectrometry is employed to directly monitor small molecule binding events to mouse GIRK2. GIRK2 binds the toxin tertiapin Q and PIPs selectively and with significantly higher affinity than other phospholipids. A mutation in GIRK2 that causes a rotation in the cytoplasmic domain, similarly to Gβγ-binding to the wild-type channel, revealed differences in the selectivity towards PIPs More specifically, PIP isoforms known to weakly activate GIRKs have decreased binding affinity. Additionally, denaturing mass spectrometry and tryptic digest liquid chromatography mass spectrometry analysis was performed to confirm phosphorylation to GIRK2.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:53:50.949.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yang Liu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-27 06:34:21	ID requested
1	2019-04-02 07:53:00	announced
⏵ 2	2024-10-22 04:53:51	announced	2024-10-22: Updated project metadata.

Liu Y, LoCaste CE, Liu W, Poltash ML, Russell DH, Laganowsky A, Selective binding of a toxin and phosphatidylinositides to a mammalian potassium channel. Nat Commun, 10(1):1352(2019) [pubmed]

10.1038/s41467-019-09333-4;

submitter keyword: Potassium Channel, PIP2, Lipid Selectivity, Lipid Binding,GIRK2, Phosphorylation

Arthur Laganowsky
contact affiliation	Texas A&M University Department of Chemistry
contact email	alaganowsky@chem.tamu.edu
lab head
Yang Liu
contact affiliation	Texas A&M University
contact email	yangalexliu@tamu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012894
     1. Label: PRIDE project
     2. Name: Selective Binding of a Toxin and Phosphatidylinositides to a Mammalian Potassium Channel