Anionic Phospholipids Shift the Conformational Equilibrium of the Selectivity Filter in the KcsA Channel to the Conductive Conformation: Predicted Consequences on Inactivation.

ABSTRACT: Here, we report an allosteric effect of an anionic phospholipid on a model K⁺ channel, KcsA. The anionic lipid in mixed detergent-lipid micelles specifically induces a change in the conformational equilibrium of the channel selectivity filter (SF) only when the channel inner gate is in the open state. Such change consists of increasing the affinity of the channel for K⁺, stabilizing a conductive-like form by maintaining a high ion occupancy in the SF. The process is highly specific in several aspects: First, lipid modifies the binding of K⁺, but not that of Na⁺, which remains unperturbed, ruling out a merely electrostatic phenomenon of cation attraction. Second, no lipid effects are observed when a zwitterionic lipid, instead of an anionic one, i

SUBMITTER: Renart ML 

PROVIDER: S-EPMC10216125 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature