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Structural and functional studies of the nicotinic acetylcholine receptor by solid-state NMR

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Abstract

Over the last seven years, solid-state NMR has been widely employed to study structural and functional aspects of the nicotinic acetylcholine receptor. These studies have provided detailed structural information relating to both the ligand binding site and the transmembrane domain of the receptor. Studies of the ligand binding domain have elucidated the nature and the orientation of the pharmacophores responsible for the binding of the agonist acetylcholine within the agonist binding site. Analyses of small transmembrane fragments derived from the nicotinic acetylcholine receptor have also revealed the secondary structure and the orientation of these transmembrane domains. These experiments have expanded our understanding of the channel’s structural properties and are providing an insight into how they might be modulated by the surrounding lipid environment. In this article we review the advances in solid-state NMR applied to the nicotinic acetylcholine receptor and compare the results with recent electron diffraction and X-ray crystallographic studies.

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Acknowledgements

S.J. Opella, F. Separovic and M.R.R. de Planque are gratefully acknowledged for helpful discussions on their latest studies on the transmembrane domain of the nicotinic acetylcholine receptor.

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Authors and Affiliations

  1. Laboratorium für Physikalische Chemie, ETH-Hönggerberg, 8093 , Zurich, Switzerland

    P. T. F. Williamson & B. H. Meier

  2. Biomembrane Structure Unit, Biochemistry Department, University of Oxford, Oxford, OX1 3QU, UK

    A. Watts

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  1. P. T. F. Williamson
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  2. B. H. Meier
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  3. A. Watts
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Correspondence to P. T. F. Williamson.

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Presented at the Biophysical Society Meeting on “Ion channels – from structure to disease” held in May 2003, Rennes, France

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Williamson, P.T.F., Meier, B.H. & Watts, A. Structural and functional studies of the nicotinic acetylcholine receptor by solid-state NMR. Eur Biophys J 33, 247–254 (2004). https://doi.org/10.1007/s00249-003-0380-1

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