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Step-wise activation of a Family C GPCR.
- Source :
-
BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 30. Date of Electronic Publication: 2023 Aug 30. - Publication Year :
- 2023
-
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 (ECD) that is linked via a cysteine-rich domain (CRDs) to their 7-transmembrane (TM) domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the ECD to the G protein-coupling TM. 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.<br />Competing Interests: Competing Interests Brian Kobilka is co-founder of and consultant for ConfometRx. The remaining authors declare no competing interest.
Details
- Language :
- English
- Database :
- MEDLINE
- Journal :
- BioRxiv : the preprint server for biology
- Accession number :
- 37693614
- Full Text :
- https://doi.org/10.1101/2023.08.29.555158