+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31599 | |||||||||
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Title | luteinizing hormone/choriogonadotropin receptor | |||||||||
Map data | ||||||||||
Sample |
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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 / 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 / arachidonic acid 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 / positive regulation of calcium-mediated signaling / ovarian follicle development / activation of adenylate cyclase activity / hormone-mediated signaling pathway / positive regulation of release of sequestered calcium ion into cytosol / adenylate cyclase-activating G protein-coupled receptor signaling pathway / cognition / male gonad development / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / 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 | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | 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 HE | |||||||||
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_31599.map.gz | 22.9 MB | EMDB map data format | |
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Header (meta data) | emd-31599-v30.xml emd-31599.xml | 10.6 KB 10.6 KB | Display Display | EMDB header |
Images | emd_31599.png | 45 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31599 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31599 | HTTPS FTP |
-Validation report
Summary document | emd_31599_validation.pdf.gz | 309.7 KB | Display | EMDB validaton report |
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Full document | emd_31599_full_validation.pdf.gz | 309.2 KB | Display | |
Data in XML | emd_31599_validation.xml.gz | 5.2 KB | Display | |
Data in CIF | emd_31599_validation.cif.gz | 5.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31599 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31599 | HTTPS FTP |
-Related structure data
Related structure data | 7fijMC 7figC 7fihC 7fiiC 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_31599.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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
Entire | Name: luteinizing hormone/choriogonadotropin receptor |
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Components |
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-Supramolecule #1: luteinizing hormone/choriogonadotropin receptor
Supramolecule | Name: luteinizing hormone/choriogonadotropin receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: Lutropin-choriogonadotropic hormone receptor
Macromolecule | Name: Lutropin-choriogonadotropic hormone receptor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 78.629797 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DYKDDDDVEN LYFQGASALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLN LSEILIQNTK NLRYIEPGAF INLPRLKYLS ICNTGIRKFP DVTKVFSSES NFILEICDNL HITTIPGNAF Q GMNNESVT ...String: DYKDDDDVEN LYFQGASALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLN LSEILIQNTK NLRYIEPGAF INLPRLKYLS ICNTGIRKFP DVTKVFSSES NFILEICDNL HITTIPGNAF Q GMNNESVT LKLYGNGFEE VQSHAFNGTT LTSLELKENV HLEKMHNGAF RGATGPKTLD ISSTKLQALP SYGLESIQRL IA TSSYSLK KLPSRETFVN LLEATLTYPS HCCAFRNLPT KEQNFSHSIS ENFSKQCEST VRKVNNKTLY SSMLAESELS GWD YEYGFC LPKTPRCAPE PDAFNPCEDI MGYDFLRVLI WLINILAIMG NMTVLFVLLT SRYKLTVPRF LMCNLSFADF CMGL YLLLI ASVDSQTKGQ YYNHAIDWQT GSGCSTAGFF TVFASELSVY TLTVITLERW HTITYAIHLD QKLRLRHAIL IMLGG WLFS SLIAMLPLVG VSNYMKVSIC FPMDVETTLS QVYILTILIL NVVAFFIICA CYIKIYFAVR NPELMATNKD TKIAKK MAI LIFTDFTCMA PISFFAISAA FKVPLITVTN SKVLLVLFYP INSCANPFLY AIFTKTFQRD FFLLLSKFGC CKRRAEL YR RKDFSAYTSN CKNGFTGSNK PSQSTLKLST LHCQGTALLD KTRYTECHHH HHHHH |
-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
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 311538 |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |