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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.
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.


Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.,Zhao LH, Lin J, Ji SY, Zhou XE, Mao C, Shen DD, He X, Xiao P, Sun J, Melcher K, Zhang Y, Yu X, Xu HE Nat Commun. 2022 Nov 5;13(1):6670. doi: 10.1038/s41467-022-33851-3. PMID:36335102<ref>PMID:36335102</ref>
, PMID:36335102<ref>PMID:36335102</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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