PDBsum entry 6pb1

Signaling protein

PDB id: 6pb1

Contents

Protein chains

281 a.a.

40 a.a.

227 a.a.

338 a.a.

57 a.a.

126 a.a.

Ligands

CLR ×4

PLM ×5

PDB id:

6pb1

Name:

Signaling protein

Title:

Cryo-em structure of urocortin 1-bound corticotropin-releasing factor 2 receptor in complex with gs protein and nb35

Structure:

Corticotropin-releasing factor receptor 2. Chain: p. Synonym: crfr-2,corticotropin-releasing hormone receptor 2,crh-r2. Engineered: yes. Urocortin. Chain: u. Engineered: yes. Guanine nucleotide-binding protein g(s) subunit alpha isoforms short,guanine nucleotide-binding protein g(i) subunit alpha-

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: crhr2, crf2r, crh2r. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Gene: gnas, gnas1, gsp, gnai1. Gene: gnb1.

Authors:

S.Ma,Q.Shen,L.-H.Zhao,C.Mao,X.E.Zhou,D.-D.Shen,P.W.De Waal,P.Bi,C.Li, Y.Jiang,M.-W.Wang,P.M.Sexton,D.Wootten,K.Melcher,Y.Zhang,H.E.Xu

Key ref:

S.Ma et al. (2020). Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors. Mol Cell, 77, 669. PubMed id: 32004470 DOI: 10.1016/j.molcel.2020.01.013

Date:

12-Jun-19 Release date: 12-Feb-20

Protein chain

Q13324  (CRFR2_HUMAN) -  Corticotropin-releasing factor receptor 2 from Homo sapiens

Seq: 411 a.a.

Struc: 281 a.a.

Protein chain

P55089  (UCN1_HUMAN) -  Urocortin from Homo sapiens

Seq: 124 a.a.

Struc: 40 a.a.

Protein chain

P63092  (GNAS2_HUMAN) -  Guanine nucleotide-binding protein G(s) subunit alpha isoforms short from Homo sapiens

Seq: 394 a.a.

Struc: 227 a.a.*

Protein chain

P63096  (GNAI1_HUMAN) -  Guanine nucleotide-binding protein G(i) subunit alpha-1 from Homo sapiens

Seq: 354 a.a.

Struc: 227 a.a.*

Protein chain

P62873  (GBB1_HUMAN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 from Homo sapiens

Seq: 340 a.a.

Struc: 338 a.a.

Protein chain

P59768  (GBG2_HUMAN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 from Homo sapiens

Seq: 71 a.a.

Struc: 57 a.a.

Protein chain

No UniProt id for this chain

Struc: 126 a.a.

* PDB and UniProt seqs differ at 156 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.3.6.5.- - ?????

DOI no: 10.1016/j.molcel.2020.01.013

Mol Cell 77:669 (2020)

PubMed id: 32004470

Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors.

S.Ma, Q.Shen, L.H.Zhao, C.Mao, X.E.Zhou, D.D.Shen, P.W.de Waal, P.Bi, C.Li, Y.Jiang, M.W.Wang, P.M.Sexton, D.Wootten, K.Melcher, Y.Zhang, H.E.Xu.

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.