Structural mechanism of lipid modulation of pentameric ligand-gated ion channel activity.

ABSTRACT: Pentameric ligand-gated ion channels (pLGICs) are sensitive to the lipid environment. However, the structural mechanism of how specific lipids support the agonist response of any pLGIC is poorly understood. Using the model pLGIC, ELIC (Erwinia ligand-gated ion channel), we find that phosphatidylethanolamine (PE) or cardiolipin (CL) are sufficient to support activation of a non-desensitizing mutant called ELIC5. Cryo-EM structures of unliganded and agonist-bound ELIC5 in the absence of PE or CL show increased structural heterogeneity and destabilization of the resting and open-channel states. Importantly, the unliganded structure of ELIC5 in a phosphatidylcholine (PC)-only environment shows variability that resembles agonist-induced changes. The structures also reveal a CL binding si

SUBMITTER: Tan BK 

PROVIDER: S-EPMC12632492 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature