Abstract：
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Ma S,Shen Q,Zhao LH,Mao C,Zhou XE,Shen DD,de Waal PW,Bi P,Li C,Jiang Y,Wang MW,Sexton PM,Wootten D,Melcher K,Zhang Y,Xu HEdoi
10.1016/j.molcel.2020.01.013subject
Has Abstractpub_date
2020-02-06 00:00:00pages
669-680.e4issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(20)30013-7journal_volume
77pub_type
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