|Title||A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Hénault, C. M., C. Govaerts, R. Spurny, M. Brams, A. Estrada-Mondragon, J. Lynch, D. Bertrand, E. Pardon, G. L. Evans, K. Woods, B. W. Elberson, L. G. Cuello, G. Brannigan, H. Nury, J. Steyaert, J. E. Baenziger, and C. Ulens|
|Journal||Nat Chem Biol|
|Date Published||2019 Dec|
Phospholipids are key components of cellular membranes and are emerging as important functional regulators of different membrane proteins, including pentameric ligand-gated ion channels (pLGICs). Here, we take advantage of the prokaryote channel ELIC (Erwinia ligand-gated ion channel) as a model to understand the determinants of phospholipid interactions in this family of receptors. A high-resolution structure of ELIC in a lipid-bound state reveals a phospholipid site at the lower half of pore-forming transmembrane helices M1 and M4 and at a nearby site for neurosteroids, cholesterol or general anesthetics. This site is shaped by an M4-helix kink and a Trp-Arg-Pro triad that is highly conserved in eukaryote GABA and glycine receptors. A combined approach reveals that M4 is intrinsically flexible and that M4 deletions or disruptions of the lipid-binding site accelerate desensitization in ELIC, suggesting that lipid interactions shape the agonist response. Our data offer a structural context for understanding lipid modulation in pLGICs.
|Alternate Journal||Nat. Chem. Biol.|
A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.