Conformational basis of G protein-coupled receptor signaling versatility
G protein-coupled receptors (GPCRs) are privileged structural scaffolds in biology that have
the versatility to regulate diverse physiological processes. Interestingly, many GPCR ligands …
the versatility to regulate diverse physiological processes. Interestingly, many GPCR ligands …
Biased ligands at opioid receptors: Current status and future directions
The opioid crisis represents a major worldwide public health crisis that has accelerated the
search for safer and more effective opioids. Over the past few years, the identification of …
search for safer and more effective opioids. Over the past few years, the identification of …
Non-canonical β-adrenergic activation of ERK at endosomes
G-protein-coupled receptors (GPCRs), the largest family of signalling receptors, as well as
important drug targets, are known to activate extracellular-signal-regulated kinase (ERK)—a …
important drug targets, are known to activate extracellular-signal-regulated kinase (ERK)—a …
Common coupling map advances GPCR-G protein selectivity
Two-thirds of human hormones and one-third of clinical drugs act on membrane receptors
that couple to G proteins to achieve appropriate functional responses. While G protein …
that couple to G proteins to achieve appropriate functional responses. While G protein …
Heterotrimeric Gq proteins act as a switch for GRK5/6 selectivity underlying β-arrestin transducer bias
Signaling-biased ligands acting on G-protein-coupled receptors (GPCRs) differentially
activate heterotrimeric G proteins and β-arrestins. Although a wealth of structural knowledge …
activate heterotrimeric G proteins and β-arrestins. Although a wealth of structural knowledge …
How Carvedilol activates β2-adrenoceptors
T Benkel, M Zimmermann, J Zeiner, S Bravo… - Nature …, 2022 - nature.com
Carvedilol is among the most effective β-blockers for improving survival after myocardial
infarction. Yet the mechanisms by which carvedilol achieves this superior clinical profile are …
infarction. Yet the mechanisms by which carvedilol achieves this superior clinical profile are …
β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells
Abstract β-arrestins mediate regulatory processes for over 800 different G protein-coupled
receptors (GPCRs) by adopting specific conformations that result from the geometry of the …
receptors (GPCRs) by adopting specific conformations that result from the geometry of the …
Community guidelines for GPCR ligand bias: IUPHAR review 32
GPCRs modulate a plethora of physiological processes and mediate the effects of one‐third
of FDA‐approved drugs. Depending on which ligand activates a receptor, it can engage …
of FDA‐approved drugs. Depending on which ligand activates a receptor, it can engage …
β-arrestin-biased allosteric modulator of NTSR1 selectively attenuates addictive behaviors
Small molecule neurotensin receptor 1 (NTSR1) agonists have been pursued for more than
40 years as potential therapeutics for psychiatric disorders, including drug addiction. Clinical …
40 years as potential therapeutics for psychiatric disorders, including drug addiction. Clinical …
Structural basis of GPCR coupling to distinct signal transducers: implications for biased signaling
Three classes of G-protein-coupled receptor (GPCR) partners–G proteins, GPCR kinases,
and arrestins–preferentially bind active GPCRs. Our analysis suggests that the structures of …
and arrestins–preferentially bind active GPCRs. Our analysis suggests that the structures of …