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PDBsum entry 7br3
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Signaling protein
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PDB id
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7br3
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References listed in PDB file
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Key reference
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Title
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Structure of the human gonadotropin-Releasing hormone receptor gnrh1r reveals an unusual ligand binding mode.
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Authors
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W.Yan,
L.Cheng,
W.Wang,
C.Wu,
X.Yang,
X.Du,
L.Ma,
S.Qi,
Y.Wei,
Z.Lu,
S.Yang,
Z.Shao.
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Ref.
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Nat Commun, 2020,
11,
5287.
[DOI no: ]
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PubMed id
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Abstract
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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.
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