All Outputs (12)

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists (2024)
Journal Article
Cullum, S. A., Platt, S., Dale, N., Isaac, O. C., Wragg, E. S., Soave, M., …Hill, S. J. (2024). Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists. Communications Biology, 7(1), Article 417. https://doi.org/10.1038/s42003-024-06128-2

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
Hoare, B. L., Tippett, D. N., Kaur, A., Cullum, S. A., Miljuš, T., Koers, E. J., …Veprintsev, D. B. (2024). ThermoBRET: A Ligand-Engagement Nanoscale Thermostability Assay Applied to GPCRs**. ChemBioChem, 25(2), Article e202300459. https://doi.org/10.1002/cbic.202300459

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
Cullum, S. A., Veprintsev, D. B., & Hill, S. J. (2023). Kinetic analysis of endogenous β2-adrenoceptor-mediated cAMP GloSensorTM responses in HEK293 cells. British Journal of Pharmacology, 180(10), 1304-1315. https://doi.org/10.1111/bph.16008

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
Jiménez-Rosés, M., Morgan, B. A., Jimenez Sigstad, M., Tran, T. D. Z., Srivastava, R., Bunsuz, A., …Veprintsev, D. B. (2022). Combined docking and machine learning identify key molecular determinants of ligand pharmacological activity on β2 adrenoceptor. Pharmacology Research and Perspectives, 10(5), Article e00994. https://doi.org/10.1002/prp2.994

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
Stoddart, L. A., Kindon, N. D., Otun, O., Harwood, C. R., Patera, F., Veprintsev, D. B., …Kellam, B. (2020). Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells. Communications Biology, 3(1), Article 722. https://doi.org/10.1038/s42003-020-01451-w

© 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
Mayer, D., Damberger, F. F., Samarasimhareddy, M., Feldmueller, M., Vuckovic, Z., Flock, T., …Veprintsev, D. B. (2019). Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation. Nature Communications, 10(1), 1-14. https://doi.org/10.1038/s41467-019-09204-y

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
Beautrait, A., Paradis, J. S., Zimmerman, B., Giubilaro, J., Nikolajev, L., Armando, S., …Bouvier, M. (2017). A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling. Nature Communications, 8, 1-16. https://doi.org/10.1038/ncomms15054

Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region (2016)
Journal Article
Venkatakrishnan, A., Deupi, X., Lebon, G., Heydenreich, F. M., Flock, T., Miljus, T., …Madan Babu, M. (2016). Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region. Nature, 536(7617), 484–487. https://doi.org/10.1038/nature19107

Backbone NMR reveals allosteric signal transduction networks in the ?1-adrenergic receptor (2016)
Journal Article
Isogai, S., Deupi, X., Opitz, C., Heydenreich, F. M., Tsai, C., Brueckner, F., …Grzesiek, S. (in press). Backbone NMR reveals allosteric signal transduction networks in the β1-adrenergic receptor. Nature, 530(7589), https://doi.org/10.1038/nature16577

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
Flock, T., Ravarani, C. N., Sun, D., Venkatakrishnan, A., Kayikci, M., Tate, C. G., …Madan Babu, M. (2015). Universal allosteric mechanism for Gα activation by GPCRs. Nature, 524(7564), https://doi.org/10.1038/nature14663

Probing G?i1 protein activation at single-amino acid resolution (2015)
Journal Article
Sun, D., Flock, T., Deupi, X., Maeda, S., Matkovic, M., Mendieta, S., …Veprintsev, D. (2015). Probing Gαi1 protein activation at single-amino acid resolution. Nature Structural and Molecular Biology, 22(9), 686–694. https://doi.org/10.1038/nsmb.3070

Hsp90-Tau Complex Reveals Molecular Basis for Specificity in Chaperone Action (2014)
Journal Article
Karagöz, G. E., Duarte, A. M., Akoury, E., Ippel, H., Biernat, J., Morán Luengo, T., …Rüdiger, S. G. (2014). Hsp90-Tau Complex Reveals Molecular Basis for Specificity in Chaperone Action. Cell, 156(5), 963-974. https://doi.org/10.1016/j.cell.2014.01.037

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.