Structure of a cholinergic cell membrane.

Abstract

While it has long been established that cell membranes are complex assemblies of proteins and bilayer-forming lipids, the inherent mobility and wide-ranging heterogeneity of the lipids have limited our ability to understand cell-membrane structure at a molecular level. Consequently, little is yet known about the protein-lipid and lipid-lipid interplay that exists in situ. Here I use cryo-EM and exploit the regularity and high protein content of the postsynaptic cell membrane of Torpedo to determine its protein-lipid structure. This membrane has a relatively simple composition, most densely populated by a single protein (nicotinic acetylcholine receptor), embedded in a cholesterol-rich phospholipid bilayer. Moreover in tubular vesicles, which bud from the isolated membranes, the protein arranges on a regular surface lattice, as it does in vivo at the Torpedo synapse and at the neuromuscular junction. Density maps obtained previously from such vesicles revealed that cholesterol attaches to specific sites on the protein in both leaflets of the bilayer, and assembles into protein-bridging aggregates or microdomains.The present study succeeds in resolving longer-range details of the lipids. Thus in the inner leaflet of the bilayer, which has the highest cholesterol concentration, the lipids are now seen to organise into close-packed linear arrays, building within the hydrophobic core a static sterol-hydrocarbon ‘skin’. This hitherto unobserved hydrophobic-core structure has far-reaching implications in terms of how cholesterol-rich membranes are constructed and function.