7E9H

Cryo-EM structure of Gi-bound metabotropic glutamate receptor mGlu4

Summary for 7E9H

• Entry DOI: 10.2210/pdb7e9h/pdb
• EMDB information: 31032
• Descriptor: Metabotropic glutamate receptor 4, Guanine nucleotide-binding protein G(i) subunit alpha-3, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total)
• Functional Keywords: mglu4, gpcr, cryo-em, complex, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 313854.03

Authors

Lin, S.,Han, S.,Zhao, Q.,Wu, B. (deposition date: 2021-03-04, release date: 2021-06-23, Last modification date: 2024-10-23)

Primary citation

Lin, S.,Han, S.,Cai, X.,Tan, Q.,Zhou, K.,Wang, D.,Wang, X.,Du, J.,Yi, C.,Chu, X.,Dai, A.,Zhou, Y.,Chen, Y.,Zhou, Y.,Liu, H.,Liu, J.,Yang, D.,Wang, M.W.,Zhao, Q.,Wu, B.
Structures of G i -bound metabotropic glutamate receptors mGlu2 and mGlu4.
Nature, 594:583-588, 2021

PubMed Abstract: The metabotropic glutamate receptors (mGlus) have key roles in modulating cell excitability and synaptic transmission in response to glutamate (the main excitatory neurotransmitter in the central nervous system). It has previously been suggested that only one receptor subunit within an mGlu homodimer is responsible for coupling to G protein during receptor activation. 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 G 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 (GPCR) structures. Furthermore, we observed an asymmetric dimer interface of the transmembrane domain of the receptor in the two mGlu-G structures. We confirmed that the asymmetric dimerization is crucial for receptor activation, which was supported by functional data; this dimerization may provide a molecular basis for the asymmetric signal transduction of mGlus. These findings offer insights into receptor signalling of class C GPCRs.

PubMed: 34135510
DOI: 10.1038/s41586-021-03495-2

Experimental method

ELECTRON MICROSCOPY (4 Å)