8T6J

CDPPB-bound inactive mGlu5

Summary for 8T6J

• Entry DOI: 10.2210/pdb8t6j/pdb
• EMDB information: 41069 41783 41787
• Descriptor: Metabotropic glutamate receptor 5, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (2 entities in total)
• Functional Keywords: gpcr, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 198465.39

Authors

Krishna Kumar, K.,Wang, H.,Kobilka, B.K. (deposition date: 2023-06-16, release date: 2023-10-11, Last modification date: 2024-10-16)

Primary citation

Krishna Kumar, K.,Wang, H.,Habrian, C.,Latorraca, N.R.,Xu, J.,O'Brien, E.S.,Zhang, C.,Montabana, E.,Koehl, A.,Marqusee, S.,Isacoff, E.Y.,Kobilka, B.K.
Stepwise activation of a metabotropic glutamate receptor.
Nature, 629:951-956, 2024

PubMed Abstract: Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging, we reveal distinct receptor conformations upon allosteric modulator and G protein binding.

PubMed: 38632403
DOI: 10.1038/s41586-024-07327-x

Experimental method

ELECTRON MICROSCOPY (3.5 Å)