Structure and gating mechanism of the acetylcholine receptor pore


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 α-helices, which curve radially to create a tapering path for the ions, and an outer ring of 15 α-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.

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Figure 1: Cross-section of a tubular crystal, at low resolution.
Figure 2: Representative portions of the polypeptide chains superimposed on the density map.
Figure 3: Pentameric structure of the pore.
Figure 4: Overview of a pore-forming subunit.
Figure 5: Lining of the pore.
Figure 6: Proposed model for the gating mechanism.


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We thank our colleagues at the MRC Laboratory, the Scripps Research Institute and Kyoto University for discussions. We particularly thank R. Henderson and A. Klug. The Marine Station at Roscoff, France, supplied the T. marmorata electric rays. This work was supported in part by a Grant-in-Aid for Specially Promoted Research, and by NEDO, the European Commission and the National Institutes of Health.

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Correspondence to Nigel Unwin.

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Miyazawa, A., Fujiyoshi, Y. & Unwin, N. Structure and gating mechanism of the acetylcholine receptor pore. Nature 423, 949–955 (2003).

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