Background: A native Kir channel in a distant relative of vertebrates interacts weakly with PIP 2 . Results: Mutagenesis restores the vertebrate channel sensitivity to PIP 2 in sponge channels. Conclusion: A basic residue in the tether helix of Kir is required for high affinity PIP 2 regulation. Significance: Evolution conferred a high affinity interaction of vertebrate Kir channels with PIP 2 , which is lacking in a distant relative.
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