6HK0

X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) F16'S pore mutant (F247S) with alternate M4 conformation.

Summary for 6HK0

• Entry DOI: 10.2210/pdb6hk0/pdb
• Descriptor: Cys-loop ligand-gated ion channel, DODECYL-BETA-D-MALTOSIDE (2 entities in total)
• Functional Keywords: ion channel, pentameric ligand-gated ion channel, cya-loop receptor, membrane protein
• Biological source: Dickeya chrysanthemi (Pectobacterium chrysanthemi)
• Total number of polymer chains: 10
• Total formula weight: 358668.73

Authors

Nury, H.,Spurny, R.,Govaerts, C.,Evans, G.L.,Pardon, E.,Steyaert, J.,Ulens, C. (deposition date: 2018-09-04, release date: 2019-10-09, Last modification date: 2024-01-17)

Primary citation

Henault, C.M.,Govaerts, C.,Spurny, R.,Brams, M.,Estrada-Mondragon, A.,Lynch, J.,Bertrand, D.,Pardon, E.,Evans, G.L.,Woods, K.,Elberson, B.W.,Cuello, L.G.,Brannigan, G.,Nury, H.,Steyaert, J.,Baenziger, J.E.,Ulens, C.
A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.
Nat.Chem.Biol., 15:1156-1164, 2019

PubMed Abstract: 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.

PubMed: 31591563
DOI: 10.1038/s41589-019-0369-4

Experimental method

X-RAY DIFFRACTION (3.45 Å)