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- PDB-7fih: luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7fih | ||||||
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Title | luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic gonadotropin-Gs-Org43553 complex | ||||||
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![]() | MEMBRANE PROTEIN / glycoprotein hormone receptor / chorionic gonadotropin / GPCR / Gs-protein | ||||||
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 / follicle-stimulating hormone activity / follicle-stimulating hormone complex / pituitary gonadotropin complex / luteinizing hormone secretion ...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 / follicle-stimulating hormone activity / follicle-stimulating hormone complex / pituitary gonadotropin complex / luteinizing hormone secretion / follicle-stimulating hormone secretion / positive regulation of steroid biosynthetic process / Thyroxine biosynthesis / Mineralocorticoid biosynthesis / positive regulation of inositol trisphosphate biosynthetic process / Hormone ligand-binding receptors / Glycoprotein hormones / Reactions specific to the complex N-glycan synthesis pathway / Androgen biosynthesis / follicle-stimulating hormone signaling pathway / ovulation cycle process / female gamete generation / cellular response to gonadotropin stimulus / positive regulation of hormone biosynthetic process / negative regulation of organ growth / cellular response to luteinizing hormone stimulus / male genitalia development / protein targeting to lysosome / thyroid hormone generation / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / G protein-coupled peptide receptor activity / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / regulation of signaling receptor activity / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / arachidonate secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / organ growth / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of calcium ion transport into cytosol / seminiferous tubule development / uterus development / peptide hormone binding / thyroid gland development / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / centriolar satellite / photoreceptor outer segment / activation of adenylate cyclase activity / ovarian follicle development / cardiac muscle cell apoptotic process / positive regulation of calcium-mediated signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / hormone-mediated signaling pathway / photoreceptor inner segment / positive regulation of release of sequestered calcium ion into cytosol / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / cognition / Golgi lumen Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 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. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 268.8 KB | Display | ![]() |
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PDB format | ![]() | 215.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 31597MC ![]() 7figC ![]() 7fiiC ![]() 7fijC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 4 types, 4 molecules ARXY
#1: Protein | Mass: 41879.465 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#4: Protein | Mass: 78655.875 Da / Num. of mol.: 1 / Mutation: S277I Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#5: Protein | Mass: 12959.992 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#6: Protein | Mass: 17755.732 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Guanine nucleotide-binding protein ... , 2 types, 2 molecules BG
#2: Protein | Mass: 38613.176 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Non-polymers , 1 types, 1 molecules ![](data/chem/img/55Z.gif)
#7: Chemical | ChemComp-55Z / |
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-Details
Has ligand of interest | N |
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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
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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
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 413532 / Symmetry type: POINT |