Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36335102.
- Also identified by DOI 10.1038/s41467-022-33851-3 and PMC identifier 9637140.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 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<sub>11</sub> and G<sub>o</sub>. We compare these structures with the structure of CRF2R in complex with G<sub>s</sub> 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.
Medical subject headings
- Heterotrimeric GTP-Binding Proteins