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Open data
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Basic information
Entry | Database: PDB / ID: 7xw7 | |||||||||
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Title | TSHR-K1-70 complex | |||||||||
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![]() | MEMBRANE PROTEIN / thyroid-stimulating hormone / thyroid-stimulating hormone receptor / THS / THSR / GPCR / Gs / k1-70 | |||||||||
Function / homology | ![]() thyroid-stimulating hormone signaling pathway / cellular response to glycoprotein / cellular response to thyrotropin-releasing hormone / thyroid-stimulating hormone receptor activity / Hormone ligand-binding receptors / G protein-coupled peptide receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hormone-mediated signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / cell-cell signaling ...thyroid-stimulating hormone signaling pathway / cellular response to glycoprotein / cellular response to thyrotropin-releasing hormone / thyroid-stimulating hormone receptor activity / Hormone ligand-binding receptors / G protein-coupled peptide receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hormone-mediated signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / cell-cell signaling / signaling receptor activity / positive regulation of cold-induced thermogenesis / G alpha (s) signalling events / basolateral plasma membrane / cell surface receptor signaling pathway / receptor complex / G protein-coupled receptor signaling pathway / positive regulation of cell population proliferation / protein-containing complex binding / cell surface / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.5 Å | |||||||||
![]() | Duan, J. / Xu, P. / Luan, X. / Ji, Y. / Yuan, Q. / He, X. / Ye, J. / Cheng, X. / Jiang, H. / Zhang, S. ...Duan, J. / Xu, P. / Luan, X. / Ji, Y. / Yuan, Q. / He, X. / Ye, J. / Cheng, X. / Jiang, H. / Zhang, S. / Jiang, Y. / Xu, H.E. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Hormone- and antibody-mediated activation of the thyrotropin receptor. Authors: Jia Duan / Peiyu Xu / Xiaodong Luan / Yujie Ji / Xinheng He / Ning Song / Qingning Yuan / Ye Jin / Xi Cheng / Hualiang Jiang / Jie Zheng / Shuyang Zhang / Yi Jiang / H Eric Xu / ![]() ![]() Abstract: Thyroid-stimulating hormone (TSH), through activation of its G-protein-coupled thyrotropin receptor (TSHR), controls the synthesis of thyroid hormone-an essential metabolic hormone. Aberrant ...Thyroid-stimulating hormone (TSH), through activation of its G-protein-coupled thyrotropin receptor (TSHR), controls the synthesis of thyroid hormone-an essential metabolic hormone. Aberrant signalling of TSHR by autoantibodies causes Graves' disease (hyperthyroidism) and hypothyroidism, both of which affect millions of patients worldwide. Here we report the active structures of TSHR with TSH and the activating autoantibody M22, both bound to the allosteric agonist ML-109, as well as an inactivated TSHR structure with the inhibitory antibody K1-70. Both TSH and M22 push the extracellular domain (ECD) of TSHR into an upright active conformation. By contrast, K1-70 blocks TSH binding and cannot push the ECD into the upright conformation. Comparisons of the active and inactivated structures of TSHR with those of the luteinizing hormone/choriogonadotropin receptor (LHCGR) reveal a universal activation mechanism of glycoprotein hormone receptors, in which a conserved ten-residue fragment (P10) from the hinge C-terminal loop mediates ECD interactions with the TSHR transmembrane domain. One notable feature is that there are more than 15 cholesterols surrounding TSHR, supporting its preferential location in lipid rafts. These structures also highlight a similar ECD-push mechanism for TSH and autoantibody M22 to activate TSHR, therefore providing the molecular basis for Graves' disease. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 127.7 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 878 KB | Display | ![]() |
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Full document | ![]() | 877.6 KB | Display | |
Data in XML | ![]() | 27.2 KB | Display | |
Data in CIF | ![]() | 40.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 33493MC ![]() 7xw5C ![]() 7xw6C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Antibody | Mass: 24400.182 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 79894.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-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
Component | Name: TSHR-thyroid stimulating hormone-Gs-ML109 complex / Type: COMPLEX / Entity ID: #2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
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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 / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 5.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 52479 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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