PDBsum entry 7br3

Signaling protein

PDB id: 7br3

Contents

Protein chain

470 a.a.

Ligands

1QW

OLC ×2

PEG ×6

FMT

F5O

PDB id:

7br3

Name:

Signaling protein

Title:

Crystal structure of the protein 1

Structure:

Gonadotropin-releasing hormone receptor,glga glycogen synthase,gonadotropin-releasing hormone receptor. Chain: a. Synonym: gnrh-r,glycogen synthase,gnrh-r. Engineered: yes. Mutation: yes. Other_details: the fusion protein of gonadotropin-releasing hormone receptor (unp residues 1-242), glga glycogen synthase (unp residues 218-413), gonadotropin-releasing hormone receptor (unp residues 257-

Source:

Homo sapiens, pyrococcus abyssi (strain ge5 / orsay). Human. Organism_taxid: 9606, 272844. Strain: ge5 / orsay. Gene: gnrhr, grhr, pab2292. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.79Å R-factor: 0.247 R-free: 0.284

Authors:

L.Cheng,Z.Shao

Key ref:

W.Yan et al. (2020). Structure of the human gonadotropin-releasing hormone receptor GnRH1R reveals an unusual ligand binding mode. Nat Commun, 11, 5287. PubMed id: 33082324 DOI: 10.1038/s41467-020-19109-w

Date:

26-Mar-20 Release date: 07-Oct-20

Protein chain

P30968  (GNRHR_HUMAN) -  Gonadotropin-releasing hormone receptor from Homo sapiens

Seq: 328 a.a.

Struc: 470 a.a.*

Protein chain

Q9V2J8  (Q9V2J8_PYRAB) -  Glycogen synthase from Pyrococcus abyssi (strain GE5 / Orsay)

Seq: 437 a.a.

Struc: 470 a.a.*

* PDB and UniProt seqs differ at 400 residue positions (black crosses)

DOI no: 10.1038/s41467-020-19109-w

Nat Commun 11:5287 (2020)

PubMed id: 33082324

Structure of the human gonadotropin-releasing hormone receptor GnRH1R reveals an unusual ligand binding mode.

W.Yan, L.Cheng, W.Wang, C.Wu, X.Yang, X.Du, L.Ma, S.Qi, Y.Wei, Z.Lu, S.Yang, Z.Shao.

ABSTRACT

Gonadotrophin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone, is the main regulator of the reproductive system, acting on gonadotropic cells by binding to the GnRH1 receptor (GnRH1R). The GnRH-GnRH1R system is a promising therapeutic target for maintaining reproductive function; to date, a number of ligands targeting GnRH1R for disease treatment are available on the market. Here, we report the crystal structure of GnRH1R bound to the small-molecule drug elagolix at 2.8 Å resolution. The structure reveals an interesting N-terminus that could co-occupy the enlarged orthosteric binding site together with elagolix. The unusual ligand binding mode was further investigated by structural analyses, functional assays and molecular docking studies. On the other hand, because of the unique characteristic of lacking a cytoplasmic C-terminal helix, GnRH1R exhibits different microswitch structural features from other class A GPCRs. In summary, this study provides insight into the ligand binding mode of GnRH1R and offers an atomic framework for rational drug design.