6PB0

Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 1 receptor in complex with Gs protein and Nb35

Summary for 6PB0

• Entry DOI: 10.2210/pdb6pb0/pdb
• EMDB information: 20284
• Descriptor: Corticotropin-releasing factor receptor 1, Urocortin, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (8 entities in total)
• Functional Keywords: corticotropin-releasing factor 1 receptor, urocortins1, gs protein, gpcr, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 156958.67

Authors

Ma, S.,Shen, Q.,Zhao, L.-H.,Mao, C.,Zhou, X.E.,Shen, D.-D.,de Waal, P.W.,Bi, P.,Li, C.,Jiang, Y.,Wang, M.-W.,Sexton, P.M.,Wootten, D.,Melcher, K.,Zhang, Y.,Xu, H.E. (deposition date: 2019-06-12, release date: 2020-02-12, Last modification date: 2024-10-23)

Primary citation

Ma, S.,Shen, Q.,Zhao, L.H.,Mao, C.,Zhou, X.E.,Shen, D.D.,de Waal, P.W.,Bi, P.,Li, C.,Jiang, Y.,Wang, M.W.,Sexton, P.M.,Wootten, D.,Melcher, K.,Zhang, Y.,Xu, H.E.
Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors.
Mol.Cell, 77:669-, 2020

PubMed 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.

PubMed: 32004470
DOI: 10.1016/j.molcel.2020.01.013

Experimental method

ELECTRON MICROSCOPY (3 Å)