1. RIKEN Harima Institute, 1-1-1 Kouto, Mikazuki-cho, Sayo, Hyogo 679-5148, Japan
2. Department of Biophysics, Faculty of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan
3. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

Correspondence to: Nigel Unwin³ Correspondence and requests for materials should be addressed to N.U. (Email: mas@mrc-lmb.cam.ac.uk). The atomic coordinates have been deposited in the Protein Data Bank with accession code 1OED. The cryo-EM map has been deposited in the 3D EM database with accession code EMD-1044.

Abstract

The nicotinic acetylcholine receptor controls electrical signalling between nerve and muscle cells by opening and closing a gated, membrane-spanning pore. Here we present an atomic model of the closed pore, obtained by electron microscopy of crystalline postsynaptic membranes. The pore is shaped by an inner ring of 5 -helices, which curve radially to create a tapering path for the ions, and an outer ring of 15 -helices, which coil around each other and shield the inner ring from the lipids. The gate is a constricting hydrophobic girdle at the middle of the lipid bilayer, formed by weak interactions between neighbouring inner helices. When acetylcholine enters the ligand-binding domain, it triggers rotations of the protein chains on opposite sides of the entrance to the pore. These rotations are communicated through the inner helices, and open the pore by breaking the girdle apart.