Lipids driving protein structure? Evolutionary adaptations in Kir channels

Many eukaryotic channels, transporters and receptors are activated by phosphatidyl inositol bisphosphate (PIP₂) in the membrane, and every member of the eukaryotic inward rectifier potassium (Kir) channel family requires membrane PIP₂ for activity. In contrast, a bacterial homolog (KirBac1.1) is specifically inhibited by PIP₂. We speculate that a key evolutionary adaptation in eukaryotic channels is the insertion of additional linkers between transmembrane and cytoplasmic domains, revealed by new crystal structures, that convert PIP₂ inhibition to activation. Such an adaptation may reflect a novel evolutionary drive to protein structure,; one that was necessary to permit channel function within the highly negatively charged membranes that evolved in the eukaryotic lineage.