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Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor

The ability to couple with multiple G protein subtypes, such as G(s), G(i/o), or G(q/11), by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in com...

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Detalles Bibliográficos
Autores principales: Zhao, Li-Hua, Lin, Jingyu, Ji, Su-Yu, Zhou, X. Edward, Mao, Chunyou, Shen, Dan-Dan, He, Xinheng, Xiao, Peng, Sun, Jinpeng, Melcher, Karsten, Zhang, Yan, Yu, Xiao, Xu, H. Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637140/
https://www.ncbi.nlm.nih.gov/pubmed/36335102
http://dx.doi.org/10.1038/s41467-022-33851-3
Descripción
Sumario:The ability to couple with multiple G protein subtypes, such as G(s), G(i/o), or G(q/11), by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with G(s) protein, have been determined. However, no structure of class B GPCRs with G(q/11) has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G(11) and G(o). We compare these structures with the structure of CRF2R in complex with G(s) to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.