+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35135 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | FSHR-Follicle stimulating hormone-compound 716340-Gs complex | |||||||||
Map data | DeepEMhancer sharpen | |||||||||
Sample |
| |||||||||
Function / homology | Function and homology information follicle-stimulating hormone receptor activity / progesterone biosynthetic process / 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 ...follicle-stimulating hormone receptor activity / progesterone biosynthetic process / 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 / Glycoprotein hormones / Hormone ligand-binding receptors / Reactions specific to the complex N-glycan synthesis pathway / Androgen biosynthesis / follicle-stimulating hormone signaling pathway / female gamete generation / Sertoli cell proliferation / gonad development / PKA activation in glucagon signalling / sensory perception of chemical stimulus / positive regulation of cAMP-mediated signaling / negative regulation of organ growth / regulation of osteoclast differentiation / cellular response to follicle-stimulating hormone stimulus / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / regulation of protein kinase A signaling / D1 dopamine receptor binding / thyroid hormone generation / G protein-coupled peptide receptor activity / regulation of signaling receptor activity / Hedgehog 'off' state / beta-2 adrenergic receptor binding / organ growth / female gonad development / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase activator activity / thyroid gland development / positive regulation of bone resorption / insulin-like growth factor receptor binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / hormone-mediated signaling pathway / ionotropic glutamate receptor binding / bone development / G-protein beta/gamma-subunit complex binding / transforming growth factor beta receptor signaling pathway / positive regulation of GTPase activity / platelet aggregation / female pregnancy / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / hormone activity / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Golgi lumen / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / male gonad development / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (12/13) signalling events / extracellular vesicle / positive regulation of cold-induced thermogenesis / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 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
| |||||||||
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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_35135.map.gz | 55.6 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-35135-v30.xml emd-35135.xml | 27.2 KB 27.2 KB | Display Display | EMDB header |
Images | emd_35135.png | 66.7 KB | ||
Others | emd_35135_additional_1.map.gz emd_35135_additional_2.map.gz emd_35135_half_map_1.map.gz emd_35135_half_map_2.map.gz | 32 MB 59.8 MB 38 MB 38 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35135 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35135 | HTTPS FTP |
-Validation report
Summary document | emd_35135_validation.pdf.gz | 528.9 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_35135_full_validation.pdf.gz | 528.5 KB | Display | |
Data in XML | emd_35135_validation.xml.gz | 11.9 KB | Display | |
Data in CIF | emd_35135_validation.cif.gz | 13.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35135 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35135 | HTTPS FTP |
-Related structure data
Related structure data | 8i2gMC 8i2hC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_35135.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | DeepEMhancer sharpen | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Additional map: Locel map on FSH and FSHR-ECD
File | emd_35135_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Locel map on FSH and FSHR-ECD | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: b-factor sharpen
File | emd_35135_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | b-factor sharpen | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_35135_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_35135_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
+Entire : FSHR-Follicle stimulating hormone-compound 716340-Gs complex
+Supramolecule #1: FSHR-Follicle stimulating hormone-compound 716340-Gs complex
+Macromolecule #1: chimera of 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: Nb35
+Macromolecule #5: Follicle-stimulating hormone receptor
+Macromolecule #6: Glycoprotein hormones alpha chain
+Macromolecule #7: Follitropin subunit beta
+Macromolecule #9: CHOLESTEROL
+Macromolecule #10: PALMITIC ACID
+Macromolecule #11: MYRISTIC ACID
+Macromolecule #12: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #13: N-tert-butyl-N-ethyl-8-methoxy-9-propan-2-yloxy-1-thiophen-2-yl-5...
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 477950 |
---|---|
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |