scholarly journals A Computationally Designed Water-Soluble Variant of a G-Protein-Coupled Receptor: The Human Mu Opioid Receptor

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66009 ◽  
Author(s):  
Jose Manuel Perez-Aguilar ◽  
Jin Xi ◽  
Felipe Matsunaga ◽  
Xu Cui ◽  
Bernard Selling ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Water Soluble ◽  
G Protein Coupled Receptor ◽  
Mu Opioid ◽  
G Protein Coupled

scholarly journals Measuring ligand efficacy at the mu-opioid receptor using a conformational biosensor

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Kathryn E Livingston ◽  
Jacob P Mahoney ◽  
Aashish Manglik ◽  
Roger K Sunahara ◽  
John R Traynor
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
G Protein Coupled Receptors ◽  
Physiological Effects ◽  
Allosteric Modulators ◽  
Mu Opioid ◽  
Class A ◽  
Orthosteric Ligands ◽  
G Protein Coupled

The intrinsic efficacy of orthosteric ligands acting at G-protein-coupled receptors (GPCRs) reflects their ability to stabilize active receptor states (R*) and is a major determinant of their physiological effects. Here, we present a direct way to quantify the efficacy of ligands by measuring the binding of a R*-specific biosensor to purified receptor employing interferometry. As an example, we use the mu-opioid receptor (µ-OR), a prototypic class A GPCR, and its active state sensor, nanobody-39 (Nb39). We demonstrate that ligands vary in their ability to recruit Nb39 to µ-OR and describe methadone, loperamide, and PZM21 as ligands that support unique R* conformation(s) of µ-OR. We further show that positive allosteric modulators of µ-OR promote formation of R* in addition to enhancing promotion by orthosteric agonists. Finally, we demonstrate that the technique can be utilized with heterotrimeric G protein. The method is cell-free, signal transduction-independent and is generally applicable to GPCRs.

scholarly journals Role for G protein-coupled receptor kinase in agonist-specific regulation of  -opioid receptor responsiveness

1998 ◽  
Vol 95 (12) ◽  
pp. 7157-7162 ◽  
Author(s):  
J. Zhang ◽  
S. S. G. Ferguson ◽  
L. S. Barak ◽  
S. R. Bodduluri ◽  
S. A. Laporte ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Specific Regulation ◽  
G Protein Coupled

Some effects of putative G-protein biased mu-opioid receptor agonists in male rhesus monkeys

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jeremy C. Cornelissen ◽  
Bruce E. Blough ◽  
Laura M. Bohn ◽  
S. Stevens Negus ◽  
Matthew L. Banks
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Rhesus Monkeys ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Receptor Agonists ◽  
Opioid Receptor Agonists ◽  
Male Rhesus

scholarly journals Characterization of an engineered water-soluble variant of the full-length human mu opioid receptor

2019 ◽  
Vol 38 (14) ◽  
pp. 4364-4370 ◽  
Author(s):  
Jin Xi ◽  
Jie Xiao ◽  
Jose Manuel Perez-Aguilar ◽  
Jinglei Ping ◽  
A.T. Charlie Johnson ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Water Soluble ◽  
Full Length ◽  
Mu Opioid
Sign in / Sign up

Export Citation Format

Share Document