Rapid and accurate mapping of ligand binding and structural changes in the β-1 adrenergic receptor using carbene footprinting and mass spectrometry
Publication Date
April 11, 2025
Description
G protein coupled receptors (GPCRs) control many physiological processes and are major targets for therapeutic intervention. As transmembrane proteins with inherent instability they are often difficult study with more conventional structural methods. Here we report the use of carbene footprinting to map ligand binding and structural changes in the β1-adrenergic receptor, β1AR, a GPCR target of beta-blocker drugs. The method revealed differences between binding of the agonist, isoprenaline, and the reverse agonist, carazalol, both in terms of their occupancy of the orthosteric ligand binding site and their effects on key regulatory structural features of β1AR including the ‘ionic lock’ between transmembrane (TM) helicies 3 and 6. Addition of nanobodies (Nbs) known to stabilise the activated complex (Nb80) and inactivated complex (Nb60) of β1AR induced further structural changes above those seen with the ligands alone. This repository entry contains the raw MS data in support of this work.
Collection dates:
2022-2023
Subjects
Subjects (JACS)
Subjects (LC)
Divisions
University of Nottingham, UK Campus::Faculty of Science::School of Chemistry
Corporate collaborators
OMass Therapeutics
Data type
Mass spectrometry (LC-MS) raw data
Grant Number
BB/M008770/1
BB/T008369/1
Data collection method
Collected on a Dionex Ultimate 3000 nanoLC connected to a Thermo LTQFT mass spectrometer
Resource languages
English
Publisher
The University of Nottingham
Date Issued
July 1, 2025
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Name
Differential.zip
Size
19.94 GB
Format
Unknown
Checksum (MD5)
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