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 phosphorylation barcode.
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.
Tegvir S. Boora, Han-Yu Chen, Aaron Cho et al.· bioRxiv· 0 citations
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.
Qian He, Li-Hua Zhao, H. E. Xu· Cell Discovery· 1 citation
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.
Dagan C. Marx, Alberto J. Gonzalez-Hernandez, Joon Lee et al.· Nature Communications· 1 citation
Biased signaling in G protein-coupled receptors offers therapeutic promise, yet rational design of biased ligands remains challenging due to limited mechanistic understanding. Here, we report a molecular basis for controlling signaling bias at the immunometabolic receptor GPR84. We identify three structurally-matched l...
Pin-Qi Wang, Xuan Zhang, Abdul-Akim Guseinov et al.· Nature Communications· 0 citations
Cryo-electron microscopy structures of GPR84 in both active and inactive states revealed how different ligands interact with GPR84, influencing its signaling pathways, and provided a structural basis for designing selective modulators of GPR84, which could lead to new therapeutic strategies for diseases involving immun...
Myung Kyung Choi, D. Park, Pankyung Kim et al.· Experimental and Molecular M...· 0 citations
It is demonstrated that p11 recruitment to GPCRs is promoted by an active receptor conformation, and p11 acts as an amplifier of endogenous PAR2 signaling.
Marcus Saarinen, Ilana B. Kotliar, Inga Höffkes et al.· Science Advances· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
