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TitleMolecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors.
Journal, issue, pagesMol Cell, Vol. 77, Issue 3, Page 669-680.e4, Year 2020
Publish dateFeb 6, 2020
AuthorsShanshan Ma / Qingya Shen / Li-Hua Zhao / Chunyou Mao / X Edward Zhou / Dan-Dan Shen / Parker W de Waal / Peng Bi / Chuntao Li / Yi Jiang / Ming-Wei Wang / Patrick M Sexton / Denise Wootten / Karsten Melcher / Yan Zhang / H Eric Xu /
PubMed AbstractCorticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of ...Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bound CRF1R and CRF2R with the stimulatory G protein. In both structures, UCN1 adopts a single straight helix with its N terminus dipped into the receptor transmembrane bundle. Although the peptide-binding residues in CRF1R and CRF2R are different from other members of class B GPCRs, the residues involved in receptor activation and G protein coupling are conserved. In addition, both structures reveal bound cholesterol molecules to the receptor transmembrane helices. Our structures define the basis of ligand-binding specificity in the CRF receptor-hormone system, establish a common mechanism of class B GPCR activation and G protein coupling, and provide a paradigm for studying membrane protein-lipid interactions for class B GPCRs.
External linksMol Cell / PubMed:32004470
MethodsEM (single particle)
Resolution2.8 - 3.0 Å
Structure data

20284

6pb0

EMDB-20284, PDB-6pb0:
Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 1 receptor in complex with Gs protein and Nb35
Method: EM (single particle) / Resolution: 3.0 Å

20285

6pb1

EMDB-20285, PDB-6pb1:
Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 2 receptor in complex with Gs protein and Nb35
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL / Cholesterol

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsSIGNALING PROTEIN / Corticotropin-releasing factor 1 receptor / urocortins1 / Gs protein / GPCR / Corticotropin-releasing factor 2 receptor

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