Selective binding of a toxin and phosphatidylinositides to a mammalian potassium channel
| Autor: | David H. Russell, Yang Liu, Arthur Laganowsky, Wen Liu, Catherine E. LoCaste, Michael L. Poltash |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Gene isoform Science General Physics and Astronomy 02 engineering and technology Gating Plasma protein binding medicine.disease_cause Phosphatidylinositols General Biochemistry Genetics and Molecular Biology Article Mass Spectrometry 03 medical and health sciences Mice medicine Animals Phosphorylation lcsh:Science Mammals Mutation Multidisciplinary Chemistry urogenital system General Chemistry 021001 nanoscience & nanotechnology Potassium channel Bee Venoms 030104 developmental biology G Protein-Coupled Inwardly-Rectifying Potassium Channels Cytoplasm Biophysics lcsh:Q lipids (amino acids peptides and proteins) Small molecule binding 0210 nano-technology Protein Binding |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-9 (2019) |
| ISSN: | 2041-1723 |
| Popis: | 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. Taken together, our results reveal selective small molecule binding and uncover a mechanism by which rotation of the cytoplasmic domain can modulate GIRK•PIP interactions. G-protein-gated inward rectifying potassium channels (GIRKs) require Gβγ subunits and phosphorylated phosphatidylinositides (PIPs) for gating. Here authors use native ion mobility mass spectrometry to monitor small molecule binding events to GIRK2 and shed light on the selectivity of GIRK2 towards PIPs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|