| Title |
Structures of Gi bound metabotropic glutamate receptors mGlu2 and mGlu4 |
| Description |
The metabotropic glutamate receptors have key roles in modulating cell excitability and synaptic transmission in response to glutamate 1 . It has previously been suggested that only one receptor subunit within an mGlu homodimer is responsible for coupling to G protein during receptor activation2 . However, the molecular mechanism that underlies the asymmetric signalling of mGlus remains unknown. Here we report two cryo electron microscopy structures of human mGlu2 and mGlu4 bound to heterotrimeric Gi protein. The structures reveal a G protein binding site formed by three intracellular loops and helices III and IV that is distinct from the corresponding binding site in all of the other G protein coupled receptor structures. Furthermore, we observed an asymmetric dimer interface of the transmembrane domain of the receptor in the two mGlu Gi structures. We confirmed that the asymmetric dimerization is crucial for receptor activation, which was supported by functional data. |
| Organism |
Homo sapiens |
| Data Type |
Protein 3D Structure Data |
| Data Accessibility |
Controlled-access |
| BioProject |
PRJCA016824 |
| Release Date |
2024-12-31 |
| Submitter |
wenru zhang (wrzhang@simm.ac.cn) |
| Organization |
Shanghai nstitute of Material Medica |
| Submission Date |
2023-05-08 |