Decoding functional specialization in G protein‐coupled receptors (GPCRs) through evolution‐guided residue profiling

Allosteric pathways govern Gα protein coupling selectivity at promiscuous GPCRs

It is suggested that Gα protein selectivity is an allosterically encoded property of GPCRs and provide a conceptual framework for designing ligands and receptors with tailored Gα protein-biased signaling.

‘Superdark’ protein looks like a G-protein-coupled receptor — but shows unconventional behaviour

Tunable AMPA receptor function via recurrent evolution of heterotetramers

AMPA receptors are glutamate receptors specific to bilaterian animals with complex nervous systems. Wang et al. investigated the biophysical function, pharmacology, and kinetics of AMPA receptors from diverse bilaterians, uncovering convergent evolution on functional hallmarks, such as heteromerization and channel prop...

Structural basis of endogenous lipid recognition and G protein selectivity in GPR119

G protein-coupled receptors (GPCRs) often engage multiple intracellular transducers, yet the structural basis by which endogenous ligands influence G protein selectivity remains poorly understood. GPR119 is a lipid-activated receptor expressed in pancreatic β-cells and enteroendocrine L-cells, where it regulates glucos...

Peptide-based therapeutics targeting GPCRs: recent applications in the treatment of metabolic disorders

G protein-coupled receptors are among the largest protein superfamilies in the human genome and are responsible for sensing diverse extracellular signals and mediating them into cellular responses. Owing to their broad range of subunits and downstream effectors regulated by specific ligands, these receptors have been a...

Configurational diversity of metabotropic glutamate receptor complexes with beta-arrestins

A single molecule pulldown (SiMPull) assay is developed that reports on both relative GPCR:β-arr interaction strength and stoichiometry to uncover molecular diversity in β-arr coupling to the neuromodulatory metabotropic glutamate receptors (mGluRs), prototypical, dimeric family C GPCRs.