PXD045464

PXD045464 is an original dataset announced via ProteomeXchange.

Title	Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-12-09
AnnouncementXML	Submission_2023-12-09_04:01:42.583.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kazem Asadollahi
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-18 06:05:59	ID requested
⏵ 1	2023-12-09 04:01:43	announced

10.1038/S41467-023-44010-7;

submitter keyword: GPCR recognition

neurotensin

coupled folding and binding, induced fit

19F-NMR

stopped-flow fluorescence.

Paul Raymond
contact affiliation	Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, VIC 3010, Australia
contact email	prg@unimelb.edu.au
lab head
Kazem Asadollahi
contact affiliation	Department of Biochemistry and Pharmacology, University of Melbourne
contact email	asadollahik@unimelb.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/12/PXD045464

PRIDE project URI

• PRIDE
  1. PXD045464
     1. Label: PRIDE project
     2. Name: Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1