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


ABSTRACT: The ability to couple with multiple G protein subtypes, such as Gs, Gi/o, or Gq/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 Gs protein, have been determined. However, no structure of class B GPCRs with Gq/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, G11 and Go. We compare these structures with the structure of CRF2R in complex with Gs 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.

SUBMITTER: Zhao LH 

PROVIDER: S-EPMC9637140 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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

Zhao Li-Hua LH   Lin Jingyu J   Ji Su-Yu SY   Zhou X Edward XE   Mao Chunyou C   Shen Dan-Dan DD   He Xinheng X   Xiao Peng P   Sun Jinpeng J   Melcher Karsten K   Zhang Yan Y   Yu Xiao X   Xu H Eric HE  

Nature communications 20221105 1


The ability to couple with multiple G protein subtypes, such as G<sub>s</sub>, G<sub>i/o</sub>, or G<sub>q/11</sub>, 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<sub>s</sub> protein, have been determined. However, no structure of class B GPCRs with G<sub>q/11</sub> has been solved to date, limiting our understanding of th  ...[more]

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