Membrane-forming phospholipids allosterically modulate native-state prolyl isomerization in a CNG channel.

ABSTRACT: Ion channel activity is intricately linked to the surrounding lipid environment, yet the molecular effects of lipid-mediated regulation remain largely understudied. Here, we show that membrane-forming phospholipids, which are known to modulate the activity of the cyclic nucleotide-gated channel SthK from Spirochaeta thermophila, exhibit effects that extend well beyond the membrane boundary. Using stopped-flow flux assays, we demonstrate that anionic lipids, which are known to promote channel opening, also affect the fast-to-slow activation ratio and the cAMP potency in SthK. Enzymatic catalysis studies confirm that this occurs by altering the cis/trans equilibrium at Pro300 in the apo state. Additionally, cryogenic electron microscopy structures of SthK reveal lipid-dependent conformationa

SUBMITTER: Newton AJ 

PROVIDER: S-EPMC12631857 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature