9Y1M
Cryo EM Structure of Full Length mGluR8 in Complex with Beta-Arrestin-1 Bound to Agonist L-AP4 and PAM VU6005649
This is a non-PDB format compatible entry.
Summary for 9Y1M
| Entry DOI | 10.2210/pdb9y1m/pdb |
| Related | 9N8Y 9N8Z |
| EMDB information | 49153 49154 72398 |
| Descriptor | Metabotropic glutamate receptor 8, (2S)-2-amino-4-phosphonobutanoic acid, (3P,8S)-3-(2,3-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (3 entities in total) |
| Functional Keywords | gpcr, metabotropic glutamate receptor, membrane protein, synaptic protein, signaling protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 204440.31 |
| 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 (3.32 Å) |
Structure validation
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