Molecular Mechanism of β-Arrestin-Biased Agonism at Seven-Transmembrane Receptors

By Éric Reiter, Seungkirl Ahn, A. Shukla, R. J. Lefkowitz. Annual Review of Pharmacology and Toxicology, 2011

598 citations recorded by the source corpus.

The concept of biased agonism has recently come to the fore with the realization that seven-transmembrane receptors (7TMRs, also known as G protein–coupled receptors, or GPCRs) activate complex signaling networks and can adopt multiple active conformations upon agonist binding. As a consequence, the “efficacy” of receptors, which was classically considered linear, is now recognized as pluridimensional. Biased agonists selectively stabilize only a subset of receptor conformations induced by the natural “unbiased” ligand, thus preferentially activating certain signaling mechanisms. Such agonists thus reveal the intriguing possibility that one can direct cellular signaling with unprecedented precision and specificity and support the notion that biased agonists may identify new classes of therapeutic agents that have fewer side effects. This review focuses on one particular class of biased ligands that has the ability to alter the balance between G protein–dependent and β-arrestin-dependent signal transduction.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c62b671d536f7420326a1a56fec8e8350371a495

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Molecular Biology

Citations in the corpus

Structural Features for Functional Selectivity at Serotonin Receptors (2013, background): “Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor.”
A Unified View of “How Allostery Works” (2014, background): “Biased agonist binding implies that GPCRs can adopt multiple active states [56].”