Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1

Kazem Asadollahi, Sunnia Rajput, Lazarus Andrew Zhang, Ching-Seng Ang, Shuai Nie, Nicholas A. Williamson, Michael D. W. Griffin, Ross A. D. Bathgate, Daniel J. Scott, Thomas R. Weikl, Guy N. L. Jameson and Paul R. Gooley ()
Additional contact information
Kazem Asadollahi: University of Melbourne
Sunnia Rajput: University of Melbourne
Lazarus Andrew Zhang: The Florey, University of Melbourne
Ching-Seng Ang: University of Melbourne
Shuai Nie: University of Melbourne
Nicholas A. Williamson: University of Melbourne
Michael D. W. Griffin: University of Melbourne
Ross A. D. Bathgate: University of Melbourne
Daniel J. Scott: University of Melbourne
Thomas R. Weikl: Max Planck Institute of Colloids and Interfaces
Guy N. L. Jameson: University of Melbourne
Paul R. Gooley: University of Melbourne

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract The conformational ensembles of G protein-coupled receptors (GPCRs) include inactive and active states. Spectroscopy techniques, including NMR, show that agonists, antagonists and other ligands shift the ensemble toward specific states depending on the pharmacological efficacy of the ligand. How receptors recognize ligands and the kinetic mechanism underlying this population shift is poorly understood. Here, we investigate the kinetic mechanism of neurotensin recognition by neurotensin receptor 1 (NTS1) using 19F-NMR, hydrogen-deuterium exchange mass spectrometry and stopped-flow fluorescence spectroscopy. Our results indicate slow-exchanging conformational heterogeneity on the extracellular surface of ligand-bound NTS1. Numerical analysis of the kinetic data of neurotensin binding to NTS1 shows that ligand recognition follows an induced-fit mechanism, in which conformational changes occur after neurotensin binding. This approach is applicable to other GPCRs to provide insight into the kinetic regulation of ligand recognition by GPCRs.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-44010-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44010-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-44010-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().