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- EMDB-30996: Structural insights into the activation of human calcium-sensing ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30996 | |||||||||
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Title | Structural insights into the activation of human calcium-sensing receptor | |||||||||
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![]() | G-protein-coupled receptor (GPCR) / Calcium-sensing receptor (CaSR) / cryo-electron microscopy (cryo-EM) / calcium ions / nanobody / STRUCTURAL PROTEIN | |||||||||
Function / homology | ![]() regulation of presynaptic membrane potential / bile acid secretion / chemosensory behavior / cellular response to peptide / response to fibroblast growth factor / cellular response to vitamin D / phosphatidylinositol-4,5-bisphosphate phospholipase C activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / calcium ion import / positive regulation of positive chemotaxis ...regulation of presynaptic membrane potential / bile acid secretion / chemosensory behavior / cellular response to peptide / response to fibroblast growth factor / cellular response to vitamin D / phosphatidylinositol-4,5-bisphosphate phospholipase C activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / calcium ion import / positive regulation of positive chemotaxis / fat pad development / cellular response to hepatocyte growth factor stimulus / amino acid binding / branching morphogenesis of an epithelial tube / positive regulation of calcium ion import / regulation of calcium ion transport / cellular response to low-density lipoprotein particle stimulus / anatomical structure morphogenesis / detection of calcium ion / positive regulation of vasoconstriction / JNK cascade / axon terminus / ossification / chloride transmembrane transport / response to ischemia / cellular response to glucose stimulus / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of insulin secretion / intracellular calcium ion homeostasis / vasodilation / integrin binding / presynaptic membrane / G alpha (i) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / basolateral plasma membrane / cellular response to hypoxia / G alpha (q) signalling events / transmembrane transporter binding / positive regulation of ERK1 and ERK2 cascade / G protein-coupled receptor signaling pathway / apical plasma membrane / neuronal cell body / positive regulation of cell population proliferation / calcium ion binding / positive regulation of gene expression / protein kinase binding / glutamatergic synapse / cell surface / protein homodimerization activity / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Geng Y / Chen XC | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into the activation of human calcium-sensing receptor. Authors: Xiaochen Chen / Lu Wang / Qianqian Cui / Zhanyu Ding / Li Han / Yongjun Kou / Wenqing Zhang / Haonan Wang / Xiaomin Jia / Mei Dai / Zhenzhong Shi / Yuying Li / Xiyang Li / Yong Geng / ![]() Abstract: Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that maintains Ca homeostasis in serum. Here, we present the cryo-electron microscopy structures of the CaSR in the inactive and ...Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that maintains Ca homeostasis in serum. Here, we present the cryo-electron microscopy structures of the CaSR in the inactive and agonist+PAM bound states. Complemented with previously reported structures of CaSR, we show that in addition to the full inactive and active states, there are multiple intermediate states during the activation of CaSR. We used a negative allosteric nanobody to stabilize the CaSR in the fully inactive state and found a new binding site for Ca ion that acts as a composite agonist with L-amino acid to stabilize the closure of active Venus flytraps. Our data show that agonist binding leads to compaction of the dimer, proximity of the cysteine-rich domains, large-scale transitions of seven-transmembrane domains, and inter- and intrasubunit conformational changes of seven-transmembrane domains to accommodate downstream transducers. Our results reveal the structural basis for activation mechanisms of CaSR and clarify the mode of action of Ca ions and L-amino acid leading to the activation of the receptor. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 118.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.8 KB 13.8 KB | Display Display | ![]() |
Images | ![]() | 43.5 KB | ||
Filedesc metadata | ![]() | 6.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 499.2 KB | Display | ![]() |
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Full document | ![]() | 498.8 KB | Display | |
Data in XML | ![]() | 6.7 KB | Display | |
Data in CIF | ![]() | 7.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7e6tMC ![]() 7e6uC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.105 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : CaSR, TNCA, Ca, PO4
Entire | Name: CaSR, TNCA, Ca, PO4 |
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Components |
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-Supramolecule #1: CaSR, TNCA, Ca, PO4
Supramolecule | Name: CaSR, TNCA, Ca, PO4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Extracellular calcium-sensing receptor
Macromolecule | Name: Extracellular calcium-sensing receptor / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 97.326094 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: YGPDQRAQKK GDIILGGLFP IHFGVAAKDQ DLKSRPESVE CIRYNFRGFR WLQAMIFAIE EINSSPALLP NLTLGYRIFD TCNTVSKAL EATLSFVAQN KIDSLNLDEF CNCSEHIPST IAVVGATGSG VSTAVANLLG LFYIPQVSYA SSSRLLSNKN Q FKSFLRTI ...String: YGPDQRAQKK GDIILGGLFP IHFGVAAKDQ DLKSRPESVE CIRYNFRGFR WLQAMIFAIE EINSSPALLP NLTLGYRIFD TCNTVSKAL EATLSFVAQN KIDSLNLDEF CNCSEHIPST IAVVGATGSG VSTAVANLLG LFYIPQVSYA SSSRLLSNKN Q FKSFLRTI PNDEHQATAM ADIIEYFRWN WVGTIAADDD YGRPGIEKFR EEAEERDICI DFSELISQYS DEEEIQHVVE VI QNSTAKV IVVFSSGPDL EPLIKEIVRR NITGKIWLAS EAWASSSLIA MPQYFHVVGG TIGFALKAGQ IPGFREFLKK VHP RKSVHN GFAKEFWEET FNCHLQEGAK GPLPVDTFLR GHEESGDRFS NSSTAFRPLC TGDENISSVE TPYIDYTHLR ISYN VYLAV YSIAHALQDI YTCLPGRGLF TNGSCADIKK VEAWQVLKHL RHLNFTNNMG EQVTFDECGD LVGNYSIINW HLSPE DGSI VFKEVGYYNV YAKKGERLFI NEEKILWSGF SREVPFSNCS RDCLAGTRKG IIEGEPTCCF ECVECPDGEY SDETDA SAC NKCPDDFWSN ENHTSCIAKE IEFLSWTEPF GIALTLFAVL GIFLTAFVLG VFIKFRNTPI VKATNRELSY LLLFSLL CC FSSSLFFIGE PQDWTCRLRQ PAFGISFVLC ISCILVKTNR VLLVFEAKIP TSFHRKWWGL NLQFLLVFLC TFMQIVIC V IWLYTAPPSS YRNQELEDEI IFITCHEGSL MALGFLIGYT CLLAAICFFF AFKSRKLPEN FNEAKFITFS MLIFFIVWI SFIPAYASTY GKFVSAVEVI AILAASFGLL ACIFFNKIYI ILFKPSRNTI EAAADYKDDD DK UniProtKB: Extracellular calcium-sensing receptor |
-Macromolecule #2: PHOSPHATE ION
Macromolecule | Name: PHOSPHATE ION / type: ligand / ID: 2 / Number of copies: 2 / Formula: PO4 |
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Molecular weight | Theoretical: 94.971 Da |
Chemical component information | ![]() ChemComp-PO4: |
-Macromolecule #3: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 6 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 4 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #5: CYCLOMETHYLTRYPTOPHAN
Macromolecule | Name: CYCLOMETHYLTRYPTOPHAN / type: ligand / ID: 5 / Number of copies: 2 / Formula: TCR |
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Molecular weight | Theoretical: 216.236 Da |
Chemical component information | ![]() ChemComp-TCR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | 2D array |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: NITROGEN |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Phase plate: ZERNIKE PHASE PLATE |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: SIDE ENTRY, EUCENTRIC / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |