PIP2 acts as an essential cofactor for KCNQ channels by mediating the allosteric coupling between the voltage-sensing domain and the pore-gate domain.
PIP2 acts as a crucial cofactor mediating the coupling between voltage-sensing and pore-gate domains in KCNQ channels, highlighting a common mechanism for lipid modulation of voltage-dependent gating.
Voltage-gated potassium (Kv) channels contain voltage-sensing (VSD) and pore-gate (PGD) structural domains. During voltage-dependent gating, conformational changes in the two domains are coupled giving rise to voltage-dependent opening of the channel. In addition to membrane voltage, KCNQ (Kv7) channel opening requires the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Recent studies suggest that PIP2 serves as a cofactor to mediate VSD-PGD coupling in KCNQ1 channels. In this review, we put these findings in the context of the current understanding of voltage-dependent gating, lipid modulation of Kv channel activation, and PIP2-regulation of KCNQ channels. We suggest that lipid-mediated coupling of functional domains is a common mechanism among KCNQ channels that may be applicable to other Kv channels and membrane proteins.
Zaydman et al. (Tue,) conducted a review in KCNQ channel function. PIP2 was evaluated. PIP2 acts as an essential cofactor for KCNQ channels by mediating the allosteric coupling between the voltage-sensing domain and the pore-gate domain.
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