Journal article

Conformational Changes in Tyrosine 11 of Neurotensin Are Required to Activate the Neurotensin Receptor 1

Fabian Bumbak, Trayder Thomas, Billy J Noonan-Williams, Tasneem M Vaid, Fei Yan, Alice R Whitehead, Shoni Bruell, Martina Kocan, Xuan Tan, Margaret A Johnson, Ross AD Bathgate, David K Chalmers, Paul R Gooley, Daniel J Scott



Cell-cell communication via endogenous peptides and their receptors is vital for controlling all aspects of human physiology and most peptides signal through G protein-coupled receptors (GPCRs). Disordered peptides bind GPCRs through complex modes for which there are few representative crystal structures. The disordered peptide neurotensin (NT) is a neuromodulator of classical neurotransmitters such as dopamine and glutamate, through activation of neurotensin receptor 1 (NTS1). While several experimental structures show how NT binds NTS1, details about the structural dynamics of NT during and after binding NTS1, or the role of peptide dynamics on receptor activation, remain obscure. Here sat..

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Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This research was supported by National Health and Medical Research Council of Australia project Grants 1100676 and 1043750 (R.A.D.B., P.R.G., and D.J.S.) and the Victorian Government Operational Infrastructure Support Program. R.A.D.B. is supported by an NHMRC Research Fellowship, and D.J.S. is supported by an NHMRC Dementia Fellowship. The authors thank Tania Ferraro and Sharon Layfield for technical assistance.