+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35136 | |||||||||
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Title | Follicle stimulating hormone receptor | |||||||||
Map data | ||||||||||
Sample |
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Keywords | FSH / FSHR / GPCR / HORMONE | |||||||||
Function / homology | Function and homology information follicle-stimulating hormone receptor activity / Hormone ligand-binding receptors / follicle-stimulating hormone signaling pathway / female gamete generation / gonad development / cellular response to follicle-stimulating hormone stimulus / regulation of protein kinase A signaling / G protein-coupled peptide receptor activity / female gonad development / hormone-mediated signaling pathway ...follicle-stimulating hormone receptor activity / Hormone ligand-binding receptors / follicle-stimulating hormone signaling pathway / female gamete generation / gonad development / cellular response to follicle-stimulating hormone stimulus / regulation of protein kinase A signaling / G protein-coupled peptide receptor activity / female gonad development / hormone-mediated signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / male gonad development / G alpha (s) signalling events / spermatogenesis / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of ERK1 and ERK2 cascade / receptor complex / G protein-coupled receptor signaling pathway / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.0 Å | |||||||||
Authors | Duan J / Xu P / Yang J / Ji Y / Zhang H / Mao C / Luan X / Jiang Y / Zhang Y / Zhang S / Xu HE | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor. Authors: Jia Duan / Peiyu Xu / Huibing Zhang / Xiaodong Luan / Jiaqi Yang / Xinheng He / Chunyou Mao / Dan-Dan Shen / Yujie Ji / Xi Cheng / Hualiang Jiang / Yi Jiang / Shuyang Zhang / Yan Zhang / H Eric Xu / Abstract: Follicle stimulating hormone (FSH) is an essential glycoprotein hormone for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes ...Follicle stimulating hormone (FSH) is an essential glycoprotein hormone for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes infertility and ovarian hyperstimulation syndrome. Here we report cryo-EM structures of FSHR in both inactive and active states, with the active structure bound to FSH and an allosteric agonist compound 21 f. The structures of FSHR are similar to other glycoprotein hormone receptors, highlighting a conserved activation mechanism of hormone-induced receptor activation. Compound 21 f formed extensive interactions with the TMD to directly activate FSHR. Importantly, the unique residue H615 in FSHR plays an essential role in determining FSHR selectivity for various allosteric agonists. Together, our structures provide a molecular basis of FSH and small allosteric agonist-mediated FSHR activation, which could inspire the design of FSHR-targeted drugs for the treatment of infertility and controlled ovarian stimulation for in vitro fertilization. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35136.map.gz | 28.4 MB | EMDB map data format | |
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Header (meta data) | emd-35136-v30.xml emd-35136.xml | 14.4 KB 14.4 KB | Display Display | EMDB header |
Images | emd_35136.png | 37.3 KB | ||
Filedesc metadata | emd-35136.cif.gz | 5.6 KB | ||
Others | emd_35136_half_map_1.map.gz emd_35136_half_map_2.map.gz | 27.6 MB 23.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35136 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35136 | HTTPS FTP |
-Validation report
Summary document | emd_35136_validation.pdf.gz | 672.8 KB | Display | EMDB validaton report |
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Full document | emd_35136_full_validation.pdf.gz | 672.4 KB | Display | |
Data in XML | emd_35136_validation.xml.gz | 10.6 KB | Display | |
Data in CIF | emd_35136_validation.cif.gz | 12.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35136 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35136 | HTTPS FTP |
-Related structure data
Related structure data | 8i2hMC 8i2gC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_35136.map.gz / Format: CCP4 / Size: 30.5 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:
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-Supplemental data
-Half map: #2
File | emd_35136_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35136_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Follicle stimulating hormone receptor
Entire | Name: Follicle stimulating hormone receptor |
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Components |
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-Supramolecule #1: Follicle stimulating hormone receptor
Supramolecule | Name: Follicle stimulating hormone receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Follicle-stimulating hormone receptor
Macromolecule | Name: Follicle-stimulating 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: 76.97193 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: LGSGCHHRIC HCSNRVFLCQ ESKVTEIPSD LPRNAIELRF VLTKLRVIQK GAFSGFGDLE KIEISQNDVL EVIEADVFSN LPKLHEIRI EKANNLLYIN PEAFQNLPNL QYLLISNTGI KHLPDVHKIH SLQKVLLDIQ DNINIHTIER NSFVGLSFES V ILWLNKNG ...String: LGSGCHHRIC HCSNRVFLCQ ESKVTEIPSD LPRNAIELRF VLTKLRVIQK GAFSGFGDLE KIEISQNDVL EVIEADVFSN LPKLHEIRI EKANNLLYIN PEAFQNLPNL QYLLISNTGI KHLPDVHKIH SLQKVLLDIQ DNINIHTIER NSFVGLSFES V ILWLNKNG IQEIHNCAFN GTQLDELNLS DNNNLEELPN DVFHGASGPV ILDISRTRIH SLPSYGLENL KKLRARSTYN LK KLPTLEK LVALMEASLT YPSHCCAFAN WRRQISELHP ICNKSILRQE VDYMTQARGQ RSSLAEDNES SYSRGFDMTY TEF DYDLCN EVVDVTCSPK PDAFNPCEDI MGYNILRVLI WFISILAITG NIIVLVILTT SQYKLTVPRF LMCNLAFADL CIGI YLLLI ASVDIHTKSQ YHNYAIDWQT GAGCDAAGFF TVFASELSVY TLTAITLERW HTITHAMQLD CKVQLRHAAS VMVMG WIFA FAAALFPIFG ISSYMKVSIC LPMDIDSPLS QLYVMSLLVL NVLAFVVICG CYIHIYLTVR NPNIVSSSSD TRIAKR MAM LIFTDFLCMA PISFFAISAS LKVPLITVSK AKILLVLFHP INSCANPFLY AIFTKNFRRD FFILLSKCGC YEMQAQI YR TETSSTVHNT HPRNGHCSSA PRVTNGSTYI LVPLSHLAQN UniProtKB: Follicle-stimulating hormone receptor |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
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: 6.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 356211 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |