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

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.
Publication status:
Published

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Publisher copy:
10.1016/s0014-5793(02)02656-x

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author


Journal:
FEBS letters More from this journal
Volume:
518
Issue:
1-3
Pages:
111-115
Publication date:
2002-05-01
DOI:
EISSN:
1873-3468
ISSN:
0014-5793


Language:
English
Keywords:
Pubs id:
pubs:100595
UUID:
uuid:1749b06c-6d63-41ce-8724-df7594b5c185
Local pid:
pubs:100595
Source identifiers:
100595
Deposit date:
2012-12-19
ARK identifier:

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