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Yorodumi- PDB-7dd6: Structure of Ca2+/L-Trp-bonnd Calcium-Sensing Receptor in active state -
+Open data
-Basic information
Entry | Database: PDB / ID: 7dd6 | ||||||
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Title | Structure of Ca2+/L-Trp-bonnd Calcium-Sensing Receptor in active state | ||||||
Components | Calcium-sensing Receptor | ||||||
Keywords | MEMBRANE PROTEIN / Calcium-Sensing Receptor / CaSR / active state | ||||||
Function / homology | TRYPTOPHAN Function and homology information | ||||||
Biological species | Gallus gallus (chicken) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Wen, T.L. / Yang, X. / Shen, Y.Q. | ||||||
Citation | Journal: Sci Adv / Year: 2021 Title: Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor. Authors: Tianlei Wen / Ziyu Wang / Xiaozhe Chen / Yue Ren / Xuhang Lu / Yangfei Xing / Jing Lu / Shenghai Chang / Xing Zhang / Yuequan Shen / Xue Yang / Abstract: Calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor (GPCR) that plays an important role in calcium homeostasis and parathyroid hormone secretion. Here, we present multiple cryo- ...Calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor (GPCR) that plays an important role in calcium homeostasis and parathyroid hormone secretion. Here, we present multiple cryo-electron microscopy structures of full-length CaSR in distinct ligand-bound states. Ligands (Ca and l-tryptophan) bind to the extracellular domain of CaSR and induce large-scale conformational changes, leading to the closure of two heptahelical transmembrane domains (7TMDs) for activation. The positive modulator (evocalcet) and the negative allosteric modulator (NPS-2143) occupy the similar binding pocket in 7TMD. The binding of NPS-2143 causes a considerable rearrangement of two 7TMDs, forming an inactivated TM6/TM6 interface. Moreover, a total of 305 disease-causing missense mutations of CaSR have been mapped to the structure in the active state, creating hotspot maps of five clinical endocrine disorders. Our results provide a structural framework for understanding the activation, allosteric modulation mechanism, and disease therapy for class C GPCRs. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7dd6.cif.gz | 291.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7dd6.ent.gz | 239 KB | Display | PDB format |
PDBx/mmJSON format | 7dd6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dd/7dd6 ftp://data.pdbj.org/pub/pdb/validation_reports/dd/7dd6 | HTTPS FTP |
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-Related structure data
Related structure data | 30645MC 7dd5C 7dd7C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 119314.234 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Gallus gallus (chicken) / Gene: CASR / Production host: Homo sapiens (human) |
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-Sugars , 2 types, 10 molecules
#2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / |
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-Non-polymers , 3 types, 10 molecules
#3: Chemical | #4: Chemical | ChemComp-CA / #6: Chemical | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Calcium-sensing Receptor from Gallus gallus with Ca2+ and L-Trp Type: CELL / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Gallus gallus (chicken) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/1 |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % |
-Electron microscopy imaging
Microscopy | Model: FEI TITAN |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 100488 / Symmetry type: POINT |
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |