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

Author

Listed:
  • Yang Liu

    (Institute of Biosciences and Technology, Texas A&M Health Science Center)

  • Catherine E. LoCaste

    (Texas A&M University)

  • Wen Liu

    (Institute of Biosciences and Technology, Texas A&M Health Science Center)

  • Michael L. Poltash

    (Texas A&M University)

  • David H. Russell

    (Texas A&M University)

  • Arthur Laganowsky

    (Texas A&M University)

Abstract

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.

Suggested Citation

  • Yang Liu & Catherine E. LoCaste & Wen Liu & Michael L. Poltash & David H. Russell & Arthur Laganowsky, 2019. "Selective binding of a toxin and phosphatidylinositides to a mammalian potassium channel," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09333-4
    DOI: 10.1038/s41467-019-09333-4
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    Cited by:

    1. Yun Zhu & Bo-Ji Peng & Smriti Kumar & Lauren Stover & Jing-Yuan Chang & Jixing Lyu & Tianqi Zhang & Samantha Schrecke & Djavdat Azizov & David H. Russell & Lei Fang & Arthur Laganowsky, 2023. "Polyamine detergents tailored for native mass spectrometry studies of membrane proteins," Nature Communications, Nature, vol. 14(1), pages 1-9, December.

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