Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 proteinCryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein

Structural highlights

7try is a 6 chain structure with sequence from Homo sapiens, Rattus norvegicus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.7Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CRFR2_HUMAN G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels.

Publication Abstract from PubMed

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. 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. Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor. Nat Commun. 2022 Nov 5;13(1):6670. PMID:36335102 doi:10.1038/s41467-022-33851-3

7try, resolution 3.70Å

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