Selective binding of a toxin and phosphatidylinositides to a mammalian potassium channel.

ABSTRACT: G-protein-gated inward rectifying potassium channels (GIRKs) require G_βγ subunits and phosphorylated phosphatidylinositides (PIPs) for gating. Although studies have provided insight into these interactions, the mechanism of how these events are modulated by G_βγ 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 G_βγ-binding to the wild-type channel, revealed differences in the selectivity towards PIPs. More specific

SUBMITTER: Liu Y 

PROVIDER: S-EPMC6430785 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature