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The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor

The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor
The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor
The conformation of the neurotransmitter acetylcholine bound to the fully functional nicotinic acetylcholine receptor embedded in its native membrane environment has been characterized by using frequency-selective recoupling solid-state NMR. Six dipolar couplings among five resolved 13C-labeled atoms of acetylcholine were measured. Bound acetylcholine adopts a bent conformation characterized with a quaternary ammonium-to-carbonyl distance of 5.1 Å. In this conformation, and with its orientation constrained to that previously determined by us, the acetylcholine could be docked satisfactorily in the agonist pocket of the agonist-bound, but not the agonist-free, crystal structure of a soluble acetylcholine-binding protein from Lymnaea stagnali. The quaternary ammonium group of the acetylcholine was determined to be within 3.9 Å of five aromatic residues and its acetyl group close to residues C187/188 of the principle and residue L112 of the complementary subunit. The observed >CGraphicO chemical shift is consistent with H bonding to the nicotinic acetylcholine receptor residues ?Y116 and ?T119 that are homologous to L112 in the soluble acetylcholine-binding protein
0027-8424
18031-18036
Williamson, P.T.F.
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Verhoeven, A.
d1a444df-c78c-4241-8fce-5ae51ba75f96
Miller, K.W.
375b4c92-89d9-45e3-96ff-b9546aed690a
Meier, B.H.
09278221-d423-4544-95fb-f12bd06201b0
Watts, A.
9d52521b-918a-4f29-aaa7-c2c3f386696f
Williamson, P.T.F.
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Verhoeven, A.
d1a444df-c78c-4241-8fce-5ae51ba75f96
Miller, K.W.
375b4c92-89d9-45e3-96ff-b9546aed690a
Meier, B.H.
09278221-d423-4544-95fb-f12bd06201b0
Watts, A.
9d52521b-918a-4f29-aaa7-c2c3f386696f

Williamson, P.T.F., Verhoeven, A., Miller, K.W., Meier, B.H. and Watts, A. (2007) The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor. Proceedings of the National Academy of Sciences of the United States of America, 104 (46), 18031-18036. (doi:10.1073/pnas.0704785104).

Record type: Article

Abstract

The conformation of the neurotransmitter acetylcholine bound to the fully functional nicotinic acetylcholine receptor embedded in its native membrane environment has been characterized by using frequency-selective recoupling solid-state NMR. Six dipolar couplings among five resolved 13C-labeled atoms of acetylcholine were measured. Bound acetylcholine adopts a bent conformation characterized with a quaternary ammonium-to-carbonyl distance of 5.1 Å. In this conformation, and with its orientation constrained to that previously determined by us, the acetylcholine could be docked satisfactorily in the agonist pocket of the agonist-bound, but not the agonist-free, crystal structure of a soluble acetylcholine-binding protein from Lymnaea stagnali. The quaternary ammonium group of the acetylcholine was determined to be within 3.9 Å of five aromatic residues and its acetyl group close to residues C187/188 of the principle and residue L112 of the complementary subunit. The observed >CGraphicO chemical shift is consistent with H bonding to the nicotinic acetylcholine receptor residues ?Y116 and ?T119 that are homologous to L112 in the soluble acetylcholine-binding protein

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Published date: 2007
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 72079
URI: http://eprints.soton.ac.uk/id/eprint/72079
ISSN: 0027-8424
PURE UUID: eccbe104-8a32-4960-889a-d80a557ba37a
ORCID for P.T.F. Williamson: ORCID iD orcid.org/0000-0002-0231-8640

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Date deposited: 20 Jan 2010
Last modified: 14 Mar 2024 02:52

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Contributors

Author: A. Verhoeven
Author: K.W. Miller
Author: B.H. Meier
Author: A. Watts

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