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Yorodumi- EMDB-31596: luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31596 | |||||||||
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Title | luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic gonadotropin-Gs complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | glycoprotein hormone receptor / luteinizing hormone / chorionic gonadotropin / GPCR / Gs-protein / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information 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 / Glycoprotein hormones / Hormone ligand-binding receptors / 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 / protein targeting to lysosome / male genitalia development / regulation of signaling receptor activity / 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 / 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 / G protein-coupled peptide receptor activity / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / 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 / G alpha (i) signalling events / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / organ growth / G alpha (q) signalling events / photoreceptor outer segment membrane / arachidonate secretion / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / positive regulation of calcium ion transport into cytosol / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / 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 / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / hormone-mediated signaling pathway / positive regulation of calcium-mediated signaling / 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 | Homo sapiens (human) / Bos taurus (cattle) / Lama glama (llama) / Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Duan J / Xu P | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nature / Year: 2021 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
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_31596.map.gz | 59.8 MB | EMDB map data format | |
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Header (meta data) | emd-31596-v30.xml emd-31596.xml | 20.3 KB 20.3 KB | Display Display | EMDB header |
Images | emd_31596.png | 56.3 KB | ||
Filedesc metadata | emd-31596.cif.gz | 6.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31596 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31596 | HTTPS FTP |
-Validation report
Summary document | emd_31596_validation.pdf.gz | 504.7 KB | Display | EMDB validaton report |
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Full document | emd_31596_full_validation.pdf.gz | 504.3 KB | Display | |
Data in XML | emd_31596_validation.xml.gz | 6 KB | Display | |
Data in CIF | emd_31596_validation.cif.gz | 6.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31596 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31596 | HTTPS FTP |
-Related structure data
Related structure data | 7figMC 7fihC 7fiiC 7fijC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_31596.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic ...
+Supramolecule #1: luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic ...
+Supramolecule #2: luteinizing hormone
+Supramolecule #3: choriogonadotropin receptor
+Supramolecule #4: chorionic gonadotropin
+Supramolecule #5: Gs protein
+Supramolecule #6: antibody
+Macromolecule #1: Engineered guanine nucleotide-binding protein G(s) subunit alpha
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Camelid antibody VHH fragment Nb35
+Macromolecule #5: Lutropin-choriogonadotropic hormone receptor
+Macromolecule #6: Glycoprotein hormones alpha chain
+Macromolecule #7: Choriogonadotropin subunit beta 3
+Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 355345 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |