9Y1N
Cryo EM Structure of Full lengthmGluR8 Bound to Agonist L-AP4 and PAM VU6005649 in complex with G proteins
This is a non-PDB format compatible entry.
Summary for 9Y1N
| Entry DOI | 10.2210/pdb9y1n/pdb |
| Related | 9N8Y 9N8Z |
| EMDB information | 49153 49154 72399 72399 |
| Descriptor | Metabotropic glutamate receptor 8, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, scFv-14, ... (7 entities in total) |
| Functional Keywords | gpcr, metabotropic glutamate receptor, membrane protein, synaptic protein, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 304462.42 |
| Authors | |
| Primary citation | Marx, D.C.,Huynh, K.,Gonzalez-Hernandez, A.J.,Strauss, A.,Rico, C.,Gallo, P.N.,Sharghi Moshtaghin, S.,Arefin, A.,Broichhagen, J.,Eliezer, D.,Khelashvili, G.,Levitz, J. Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: 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 desensitized by β-arrestins (β-arrs) is not well understood. Here, we use an integrative biophysical and structural approach to probe the coupling of mGluR8 and β-arrs. Using negative stain electron microscopy (EM), we identify tail- and core-bound orientations and stoichiometries of mGluR8/β-arr complexes. Cryo-EM structures of mGluR8 alone or bound to either G proteins or β-arr1 reveal mGluR8 active states with transducer-specific differences. The mGluR8/β-arr structure shows a distinct complex orientation compared to other GPCR/β-arr structures which supports a steric mechanism of mGluR desensitization involving interactions with both subunits and the lipid bilayer. Coupling of mGluR8 to β-arr1 in an active-like conformation is verified by live-cell and single molecule FRET analysis. Finally, molecular dynamics simulations further define the positioning and dynamics of mGluR8-bound β-arr1 and the importance of critical mGluR8 residues for stabilizing β-arr1 complexes. Together, our data provide a framework for agonist-driven family C GPCR/β-arr coupling. PubMed: 42722693DOI: 10.1038/s41467-026-77556-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (6.18 Å) |
Structure validation
Download full validation report
