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TitleStructure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 6670, Year 2022
Publish dateNov 5, 2022
AuthorsLi-Hua Zhao / Jingyu Lin / Su-Yu Ji / X Edward Zhou / Chunyou Mao / Dan-Dan Shen / Xinheng He / Peng Xiao / Jinpeng Sun / Karsten Melcher / Yan Zhang / Xiao Yu / H Eric Xu /
PubMed AbstractThe ability to couple with multiple G protein subtypes, such as G, G, or G, by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the ...The ability to couple with multiple G protein subtypes, such as G, G, or G, 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 protein, have been determined. However, no structure of class B GPCRs with G 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 and G. We compare these structures with the structure of CRF2R in complex with G 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.
External linksNat Commun / PubMed:36335102 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.7 Å
Structure data

26103

7try

EMDB-26103, PDB-7try:
Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein
Method: EM (single particle) / Resolution: 3.7 Å

26104

7ts0

EMDB-26104, PDB-7ts0:
Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric Go protein
Method: EM (single particle) / Resolution: 2.8 Å

Source
  • homo sapiens (human)
  • rattus norvegicus (Norway rat)
  • synthetic construct (others)
KeywordsSIGNALING PROTEIN / GPCR / corticotropin releasing factor receptor 2 / Urocortin 1 / G11 protein / Go protein

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