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Open data
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Basic information
Entry | Database: PDB / ID: 7fij | ||||||
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Title | luteinizing hormone/choriogonadotropin receptor | ||||||
![]() | Lutropin-choriogonadotropic hormone receptor | ||||||
![]() | MEMBRANE PROTEIN / glycoprotein hormone receptor / GPCR / luteinizing hormone / choriogonadotropin receptor | ||||||
Function / homology | ![]() luteinizing hormone receptor activity / choriogonadotropin hormone receptor activity / choriogonadotropin hormone binding / regulation of steroid hormone biosynthetic process / development of secondary male sexual characteristics / luteinizing hormone signaling pathway / positive regulation of inositol trisphosphate biosynthetic process / Hormone ligand-binding receptors / ovulation cycle process / cellular response to gonadotropin stimulus ...luteinizing hormone receptor activity / choriogonadotropin hormone receptor activity / choriogonadotropin hormone binding / regulation of steroid hormone biosynthetic process / development of secondary male sexual characteristics / luteinizing hormone signaling pathway / positive regulation of inositol trisphosphate biosynthetic process / Hormone ligand-binding receptors / ovulation cycle process / cellular response to gonadotropin stimulus / positive regulation of hormone biosynthetic process / cellular response to luteinizing hormone stimulus / male genitalia development / protein targeting to lysosome / G protein-coupled peptide receptor activity / arachidonate secretion / positive regulation of calcium ion transport into cytosol / seminiferous tubule development / uterus development / peptide hormone binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / centriolar satellite / hormone-mediated signaling pathway / activation of adenylate cyclase activity / ovarian follicle development / positive regulation of calcium-mediated signaling / positive regulation of release of sequestered calcium ion into cytosol / adenylate cyclase-activating G protein-coupled receptor signaling pathway / cognition / male gonad development / ATPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (s) signalling events / spermatogenesis / receptor complex / endosome / response to xenobiotic stimulus / G protein-coupled receptor signaling pathway / extracellular space / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||
![]() | Duan, J. / Xu, P. / Cheng, X. / Mao, C. / Croll, T. / He, X. / Shi, J. / Luan, X. / Yin, W. / You, E. ...Duan, J. / Xu, P. / Cheng, X. / Mao, C. / Croll, T. / He, X. / Shi, J. / Luan, X. / Yin, W. / You, E. / Liu, Q. / Zhang, S. / Jiang, H. / Zhang, Y. / Jiang, Y. / Xu, H.E. | ||||||
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![]() | ![]() Title: Structures of full-length glycoprotein hormone receptor signalling complexes. Authors: Jia Duan / Peiyu Xu / Xi Cheng / Chunyou Mao / Tristan Croll / Xinheng He / Jingjing Shi / Xiaodong Luan / Wanchao Yin / Erli You / Qiufeng Liu / Shuyang Zhang / Hualiang Jiang / Yan Zhang / ...Authors: Jia Duan / Peiyu Xu / Xi Cheng / Chunyou Mao / Tristan Croll / Xinheng He / Jingjing Shi / Xiaodong Luan / Wanchao Yin / Erli You / Qiufeng Liu / Shuyang Zhang / Hualiang Jiang / Yan Zhang / Yi Jiang / H Eric Xu / ![]() ![]() Abstract: Luteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone. Luteinizing hormone and chorionic ...Luteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone. Luteinizing hormone and chorionic gonadotropin are essential to human reproduction and are important therapeutic drugs. They activate the same G-protein-coupled receptor, luteinizing hormone-choriogonadotropin receptor (LHCGR), by binding to the large extracellular domain. Here we report four cryo-electron microscopy structures of LHCGR: two structures of the wild-type receptor in the inactive and active states; and two structures of the constitutively active mutated receptor. The active structures are bound to chorionic gonadotropin and the stimulatory G protein (G), and one of the structures also contains Org43553, an allosteric agonist. The structures reveal a distinct 'push-and-pull' mechanism of receptor activation, in which the extracellular domain is pushed by the bound hormone and pulled by the extended hinge loop next to the transmembrane domain. A highly conserved 10-residue fragment (P10) from the hinge C-terminal loop at the interface between the extracellular domain and the transmembrane domain functions as a tethered agonist to induce conformational changes in the transmembrane domain and G-protein coupling. Org43553 binds to a pocket of the transmembrane domain and interacts directly with P10, which further stabilizes the active conformation. Together, these structures provide a common model for understanding the signalling of glycoprotein hormone receptors and a basis for drug discovery for endocrine diseases. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 103.9 KB | Display | ![]() |
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PDB format | ![]() | 70.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 31599MC ![]() 7figC ![]() 7fihC ![]() 7fiiC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 78629.797 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: luteinizing hormone/choriogonadotropin receptor / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 311538 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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