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

abstract

• G-protein-gated inward rectifying potassium channels (GIRKs) require G 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 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-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. Taken together, our results reveal selective small molecule binding and uncover a mechanism by which rotation of the cytoplasmic domain can modulate GIRKPIP interactions.

authors

• Laganowsky, Arthur
• Russell, David

published proceedings

• Nat Commun

altmetric score

• 0.5

author list (cited authors)

• Liu, Y., LoCaste, C. E., Liu, W., Poltash, M. L., Russell, D. H., & Laganowsky, A.

citation count

• 22

complete list of authors

• Liu, Yang||LoCaste, Catherine E||Liu, Wen||Poltash, Michael L||Russell, David H||Laganowsky, Arthur

publication date

• January 2019

publisher

• Springer Nature  Publisher

published in

• Nature Communications  Journal

keywords

• Animals
• Bee Venoms
• G Protein-coupled Inwardly-rectifying Potassium Channels
• Mammals
• Mass Spectrometry
• Mice
• Mutation
• Phosphatidylinositols
• Phosphorylation
• Protein Binding

Digital Object Identifier (DOI)

• 10.1038/s41467-019-09333-4

start page

• 1352

volume

• 10

issue

• 1

URL

• http://dx.doi.org/10.1038/s41467-019-09333-4