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.
|State||Published - 2010|
- Inward rectifier