All Outputs (12)

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists (2024)
Journal Article

The concept of agonist-independent signalling that can be attenuated by inverse agonists is a fundamental element of the cubic ternary complex model of G protein-coupled receptor (GPCR) activation. This model shows how a GPCR can exist in two conform... Read More about Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists.

ThermoBRET: A Ligand-Engagement Nanoscale Thermostability Assay Applied to GPCRs** (2023)
Journal Article

Measurements of membrane protein thermostability reflect ligand binding. Current thermostability assays often require protein purification or rely on pre-existing radiolabelled or fluorescent ligands, limiting their application to established targets... Read More about ThermoBRET: A Ligand-Engagement Nanoscale Thermostability Assay Applied to GPCRs**.

Kinetic analysis of endogenous β2-adrenoceptor-mediated cAMP GloSensorTM responses in HEK293 cells (2022)
Journal Article

Background and Aim: Standard pharmacological analysis of agonist activity utilises measurements of receptor-mediated responses at a set time-point, or at the peak response level, to characterise ligands. However, the occurrence of non-equilibrium con... Read More about Kinetic analysis of endogenous β2-adrenoceptor-mediated cAMP GloSensorTM responses in HEK293 cells.

Combined docking and machine learning identify key molecular determinants of ligand pharmacological activity on β2 adrenoceptor (2022)
Journal Article

G protein-coupled receptors (GPCRs) are valuable therapeutic targets for many diseases. A central question of GPCR drug discovery is to understand what determines the agonism or antagonism of ligands that bind them. Ligands exert their action via the... Read More about Combined docking and machine learning identify key molecular determinants of ligand pharmacological activity on β2 adrenoceptor.

Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells (2020)
Journal Article

© 2020, The Author(s). To study the localisation of G protein-coupled receptors (GPCR) in their native cellular environment requires their visualisation through fluorescent labelling. To overcome the requirement for genetic modification of the recept... Read More about Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells.

Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation (2019)
Journal Article

Cellular functions of arrestins are determined in part by the pattern of phosphorylation on the G protein-coupled receptors (GPCRs) to which arrestins bind. Despite high-resolution structural data of arrestins bound to phosphorylated receptor C-termi... Read More about Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation.

A new inhibitor of the ?-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling. (2017)
Journal Article

Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region (2016)
Journal Article

Backbone NMR reveals allosteric signal transduction networks in the ?1-adrenergic receptor (2016)
Journal Article

G protein-coupled receptors (GPCRs) are physiologically important transmembrane signalling proteins that trigger intracellular responses upon binding of extracellular ligands. Despite recent breakthroughs in GPCR crystallography1–3, the details of li... Read More about Backbone NMR reveals allosteric signal transduction networks in the ?1-adrenergic receptor.

Universal allosteric mechanism for G? activation by GPCRs (2015)
Journal Article

Probing G?i1 protein activation at single-amino acid resolution (2015)
Journal Article

Hsp90-Tau Complex Reveals Molecular Basis for Specificity in Chaperone Action (2014)
Journal Article

Protein folding in the cell relies on the orchestrated action of conserved families of molecular chaperones, the Hsp70 and Hsp90 systems. Hsp70 acts early and Hsp90 late in the folding path, yet the molecular basis of this timing is enigmatic, mainly... Read More about Hsp90-Tau Complex Reveals Molecular Basis for Specificity in Chaperone Action.