Stepwise activation of a metabotropic glutamate receptor.
Nature
; 629(8013): 951-956, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38632403
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 domain1. 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 domain2. 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptor de Glutamato Metabotrópico 5
/
Domínios Proteicos
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Ligantes
Limite:
Humans
Idioma:
En
Revista:
Nature
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos