27TM

GRM1-Acc State Conformation 2

This is a non-PDB format compatible entry.

Replaces:  9WQP

Summary for 27TM

• Entry DOI: 10.2210/pdb27tm/pdb
• EMDB information: 81411
• Descriptor: Metabotropic glutamate receptor 1, GAMMA-L-GLUTAMIC ACID, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: receptor, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 197913.11

Authors

Lu, Y.,Wen, T.L.,Shen, Y.Q.,Yang, X. (deposition date: 2026-06-11, release date: 2026-06-24, Last modification date: 2026-07-22)

Primary citation

Lu, Y.,Wen, T.,Lu, X.,Zhang, G.,Meng, T.,Liu, T.,Wang, X.,Shen, Y.,Yang, X.
G protein selectivity in group I metabotropic glutamate receptors.
Sci Adv, 12:eaee0044-eaee0044, 2026

PubMed Abstract: Metabotropic glutamate (mGlu) receptors are class C G protein-coupled receptor involved in synaptic transmission and neurological disorders. Group I mGlu receptors (mGlu1 and mGlu5) predominantly couple to G, whereas group II and III receptors primarily engage G. Although G-coupling mechanisms have been defined for several group II/III receptors, how group I receptors preferentially engage G remains unclear. Here we report cryo-electron microscopy structures of active mGlu-G protein complexes (mGlu1-G, mGlu1-G, mGlu5-G, and mGlu5-G) bound to l-glutamate and positive allosteric modulators (PAMs), together with two additional activated-state structures of mGlu1. Comparative structural and biochemical analyses identify a group I-specific ICL2 insertion that promotes preferential G engagement. Each receptor dimer asymmetrically binds one G protein heterotrimer via an intracellular pocket engaging the Gα amino-terminal helix. PAM binding to one 7TM domain induces W rotation and TM6 outward movement, bringing the two 7TMs into closer. These findings provide a structural basis for preferential G engagement and activation of group I mGlu receptors.

PubMed: 42430471
DOI: 10.1126/sciadv.aee0044

Experimental method

ELECTRON MICROSCOPY (3.2 Å)