The University of Southampton
University of Southampton Institutional Repository

Dynamics and orientation of N+(CD3)3-bromoacetylcholine bound to its binding site on the nicotinic acetylcholine receptor.

Dynamics and orientation of N+(CD3)3-bromoacetylcholine bound to its binding site on the nicotinic acetylcholine receptor.
Dynamics and orientation of N+(CD3)3-bromoacetylcholine bound to its binding site on the nicotinic acetylcholine receptor.
Dynamic and structural information has been obtained for an analogue of acetylcholine while bound to the agonist binding site on the nicotinic acetylcholine receptor (nAcChoR), using wide-line deuterium solid-state NMR. Analysis of the deuterium lineshape obtained at various temperatures from unoriented nAcChoR membranes labeled with deuterated bromoacetylcholine (BAC) showed that the quaternary ammonium group of the ligand is well constrained within the agonist binding site when compared with the dynamics observed in the crystalline solids. This motional restriction would suggest that a high degree of complementarity exists between the quaternary ammonium group of the ligand and the protein within the agonist binding site. nAcChoR membranes were uniaxially oriented by isopotential centrifugation as determined by phosphorous NMR of the membrane phospholipids. Analysis of the deuterium NMR lineshape of these oriented membranes enriched with the nAcChoR labeled with N+(CD3)3-BAC has enabled us to determine that the angle formed between the quaternary ammonium group of the BAC and the membrane normal is 42° in the desensitized form of the receptor. This measurement allows us to orient in part the bound ligand within the proposed receptor binding site.
0027-8424
2346-2351
Williamson, P.T.F
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Watts, J.A
b06819fc-61a2-4b7c-8d51-9f0829b1212d
Addona, G.H.
99bbc3d7-a70d-4f11-8ed9-bd8a3433757f
Miller, K.W.
375b4c92-89d9-45e3-96ff-b9546aed690a
Watts, A.
9d52521b-918a-4f29-aaa7-c2c3f386696f
Williamson, P.T.F
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Watts, J.A
b06819fc-61a2-4b7c-8d51-9f0829b1212d
Addona, G.H.
99bbc3d7-a70d-4f11-8ed9-bd8a3433757f
Miller, K.W.
375b4c92-89d9-45e3-96ff-b9546aed690a
Watts, A.
9d52521b-918a-4f29-aaa7-c2c3f386696f

Williamson, P.T.F, Watts, J.A, Addona, G.H., Miller, K.W. and Watts, A. (2001) Dynamics and orientation of N+(CD3)3-bromoacetylcholine bound to its binding site on the nicotinic acetylcholine receptor. Proceedings of the National Academy of Sciences of the United States of America, 98 (5), 2346-2351. (doi:10.1073/pnas.031361698).

Record type: Article

Abstract

Dynamic and structural information has been obtained for an analogue of acetylcholine while bound to the agonist binding site on the nicotinic acetylcholine receptor (nAcChoR), using wide-line deuterium solid-state NMR. Analysis of the deuterium lineshape obtained at various temperatures from unoriented nAcChoR membranes labeled with deuterated bromoacetylcholine (BAC) showed that the quaternary ammonium group of the ligand is well constrained within the agonist binding site when compared with the dynamics observed in the crystalline solids. This motional restriction would suggest that a high degree of complementarity exists between the quaternary ammonium group of the ligand and the protein within the agonist binding site. nAcChoR membranes were uniaxially oriented by isopotential centrifugation as determined by phosphorous NMR of the membrane phospholipids. Analysis of the deuterium NMR lineshape of these oriented membranes enriched with the nAcChoR labeled with N+(CD3)3-BAC has enabled us to determine that the angle formed between the quaternary ammonium group of the BAC and the membrane normal is 42° in the desensitized form of the receptor. This measurement allows us to orient in part the bound ligand within the proposed receptor binding site.

This record has no associated files available for download.

More information

Published date: 27 February 2001
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 45393
URI: http://eprints.soton.ac.uk/id/eprint/45393
ISSN: 0027-8424
PURE UUID: 7a78a8df-2ca0-4ac1-99e4-fcb3411ba73b
ORCID for P.T.F Williamson: ORCID iD orcid.org/0000-0002-0231-8640

Catalogue record

Date deposited: 27 Mar 2007
Last modified: 16 Mar 2024 03:53

Export record

Altmetrics

Contributors

Author: J.A Watts
Author: G.H. Addona
Author: K.W. Miller
Author: A. Watts

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×