β-arrestin1 directly engages Gαs to sustain endosomal GPCR signaling

Structural basis of β-arrestin coupling and transducer selectivity in PAC1R.

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.

Arrestins as programmable integrators of GPCR signaling: structural microstates, spatiotemporal logic, and therapeutic control

Recent structural, biochemical, and physiological insights are synthesized to outline how arrestins decode regulatory inputs into signaling outcomes and how this knowledge enables the development of next-generation, structure-guided GPCR therapeutics.

Sparsely Phosphorylable Residues, Tuned by Agonist Chemotype, Shapes GPCR Signaling

It is shown that the melanocortin-4 receptor (MC4R), a central regulator of energy homeostasis, achieves remarkably diverse and pathway-selective signaling through a sparse set of strategically positioned regulatory phosphoresidues, arguing that GPCR signaling diversity does not necessarily require an extensive phospho...

Tools to investigate class B1 GPCR conformational landscapes with cryo-EM and beyond.

G protein-coupled receptors (GPCRs) are membrane proteins that act as signal transducers across cell membranes. Class B1 GPCRs, a subset of 15 receptors activated by peptide hormones, are involved in important physiological processes and diseases, making them a popular target for drug development. GPCRs are dynamic pro...

Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins

Metabotropic glutamate receptors (mGluRs) are prototypical, dimeric family C G protein-coupled receptors (GPCR) that perform crucial modulatory roles throughout the nervous system. While mGluR activation and signaling through G proteins has been studied extensively, how these receptors interact with and are desensitize...