Probing the environment of neurotensin whilst bound to the neurotensin receptor by solid state NMR


Williamson, P.T.F., Bains, S., Chung, C., Cooke, R. and Watts, A. (2002) Probing the environment of neurotensin whilst bound to the neurotensin receptor by solid state NMR. FEBS Letters, 518, (1-3), 111-115. (doi:10.1016/S0014-5793(02)02656-X).

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Description/Abstract

A functionally active analogue of neurotensin, neurotensin(8–13), has been observed whilst bound to the agonist-binding site of the rat neurotensin receptor by nuclear magnetic resonance (NMR). Through the application of slow magic angle sample spinning and high-power proton decoupling, sufficient resolution and sensitivity were obtained in the carbon-13 spectrum to allow an assignment of many of the side chain resonances arising from uniformly carbon-13/nitrogen-15-labelled neurotensin(8–13) whilst bound to the neurotensin receptor. Significant perturbations in carbon-13 chemical shift were observed upon the binding of the neurotensin(8–13) to the receptor. Most importantly significant shifts were observed in both the carboxy terminus and tyrosine side chain of the neurotensin(8–13), suggesting that these sites are important in the interaction of the neurotensin with the agonist-binding site on the neurotensin receptor. Conversely, no perturbations were observed for the carbon-13 sites within the guanidinium groups of the arginine side chains, indicating little interaction with the receptor-binding site, or a shielding of the local environment by the surrounding nitrogen atoms. These NMR observations lend further support to previous structure–activity studies, site-directed mutagenesis and modelling studies of the agonist-binding site of the neurotensin receptor, from which the same specific residues for which NMR perturbations were observed are important for neurotensin receptor activation by neurotensin.

Item Type: Article
ISSNs: 0014-5793 (print)
Related URLs:
Keywords: neurotensin, protein expression, solid state, MAS, nuclear magnetic resonance, G-protein coupled receptor
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 56039
Date Deposited: 07 Aug 2008
Last Modified: 27 Mar 2014 18:38
URI: http://eprints.soton.ac.uk/id/eprint/56039

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