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Yorodumi- EMDB-43811: Structure of human calcium-sensing receptor in complex with chime... -
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-Basic information
Entry | Database: EMDB / ID: EMD-43811 | |||||||||
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Title | Structure of human calcium-sensing receptor in complex with chimeric Gq (miniGisq) protein in nanodiscs | |||||||||
Map data | Human CaSR-miniGis complex in nanodiscs, composite map of locally refined CaSR ECD, CaSR TMD and G protein | |||||||||
Sample |
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Keywords | Calcium-sensing receptor / G-protein-coupled receptor / G protein / signal transduction / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information bile acid secretion / chemosensory behavior / cellular response to peptide / response to fibroblast growth factor / cellular response to vitamin D / phosphatidylinositol phospholipase C activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / calcium ion import / positive regulation of positive chemotaxis / fat pad development ...bile acid secretion / chemosensory behavior / cellular response to peptide / response to fibroblast growth factor / cellular response to vitamin D / phosphatidylinositol phospholipase C activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / calcium ion import / positive regulation of positive chemotaxis / fat pad development / amino acid binding / cellular response to hepatocyte growth factor stimulus / 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 / detection of calcium ion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / anatomical structure morphogenesis / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / axon terminus / regulation of mitotic spindle organization / cellular response to forskolin / JNK cascade / positive regulation of vasoconstriction / chloride transmembrane transport / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / ossification / Regulation of insulin secretion / G protein-coupled receptor binding / response to ischemia / G protein-coupled receptor activity / cellular response to glucose stimulus / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / positive regulation of insulin secretion / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / response to peptide hormone / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / intracellular calcium ion homeostasis / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / vasodilation / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / GDP binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / integrin binding / retina development in camera-type eye / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / cellular response to hypoxia / G alpha (s) signalling events / G alpha (q) signalling events / basolateral plasma membrane / Ras protein signal transduction / cell population proliferation / transmembrane transporter binding / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / cell cycle Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Zuo H / Park J / Frangaj A / Ye J / Lu G / Manning JJ / Asher WB / Lu Z / Hu G / Wang L ...Zuo H / Park J / Frangaj A / Ye J / Lu G / Manning JJ / Asher WB / Lu Z / Hu G / Wang L / Mendez J / Eng E / Zhang Z / Lin X / Grasucci R / Hendrickson WA / Clarke OB / Javitch JA / Conigrave AD / Fan QR | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2024 Title: Promiscuous G-protein activation by the calcium-sensing receptor. Authors: Hao Zuo / Jinseo Park / Aurel Frangaj / Jianxiang Ye / Guanqi Lu / Jamie J Manning / Wesley B Asher / Zhengyuan Lu / Guo-Bin Hu / Liguo Wang / Joshua Mendez / Edward Eng / Zhening Zhang / ...Authors: Hao Zuo / Jinseo Park / Aurel Frangaj / Jianxiang Ye / Guanqi Lu / Jamie J Manning / Wesley B Asher / Zhengyuan Lu / Guo-Bin Hu / Liguo Wang / Joshua Mendez / Edward Eng / Zhening Zhang / Xin Lin / Robert Grassucci / Wayne A Hendrickson / Oliver B Clarke / Jonathan A Javitch / Arthur D Conigrave / Qing R Fan / Abstract: The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca concentration and maintains Ca homeostasis. It also mediates diverse cellular processes not associated with Ca ...The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca concentration and maintains Ca homeostasis. It also mediates diverse cellular processes not associated with Ca balance. The functional pleiotropy of CaSR arises in part from its ability to signal through several G-protein subtypes. We determined structures of CaSR in complex with G proteins from three different subfamilies: G, G and G. We found that the homodimeric CaSR of each complex couples to a single G protein through a common mode. This involves the C-terminal helix of each Gα subunit binding to a shallow pocket that is formed in one CaSR subunit by all three intracellular loops (ICL1-ICL3), an extended transmembrane helix 3 and an ordered C-terminal region. G-protein binding expands the transmembrane dimer interface, which is further stabilized by phospholipid. The restraint imposed by the receptor dimer, in combination with ICL2, enables G-protein activation by facilitating conformational transition of Gα. We identified a single Gα residue that determines G and G versus G selectivity. The length and flexibility of ICL2 allows CaSR to bind all three Gα subtypes, thereby conferring capacity for promiscuous G-protein coupling. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_43811.map.gz | 10.7 MB | EMDB map data format | |
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Header (meta data) | emd-43811-v30.xml emd-43811.xml | 27.5 KB 27.5 KB | Display Display | EMDB header |
Images | emd_43811.png | 99.2 KB | ||
Filedesc metadata | emd-43811.cif.gz | 8.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-43811 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43811 | HTTPS FTP |
-Related structure data
Related structure data | 9asbMC 9avgC 9avlC 9axfC 9ayfC C: citing same article (ref.) M: atomic model generated by this map |
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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_43811.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Human CaSR-miniGis complex in nanodiscs, composite map of locally refined CaSR ECD, CaSR TMD and G protein | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
+Entire : Human CaSR in complex with chimeric Gq (miniGisq) protein
+Supramolecule #1: Human CaSR in complex with chimeric Gq (miniGisq) protein
+Macromolecule #1: Isoform 1 of Extracellular calcium-sensing receptor
+Macromolecule #2: Chimeric mini guanine nucleotide-binding protein G(i)(s)(q) subun...
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Chimeric mini guanine nucleotide-binding protein G(i)(s)(q) subun...
+Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #7: CYCLOMETHYLTRYPTOPHAN
+Macromolecule #8: PHOSPHATE ION
+Macromolecule #9: CALCIUM ION
+Macromolecule #10: 3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]propan-1-amine
+Macromolecule #11: CHOLESTEROL HEMISUCCINATE
+Macromolecule #12: (19R,22S,25R)-22,25,26-trihydroxy-16,22-dioxo-17,21,23-trioxa-22l...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3.6 mg/mL | |||||||||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R0.6/1 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Support film - Film thickness: 50 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 25 sec. / Pretreatment - Atmosphere: OTHER | |||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV Details: The sample was blotted for 6s before plunge-frozen.. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 1.9000000000000001 µm / Nominal defocus min: 1.2 µm / Nominal magnification: 105000 |
Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 15 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Temperature | Max: 100.0 K |
Software | Name: EPU |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Digitization - Dimensions - Width: 11520 pixel / Digitization - Dimensions - Height: 8184 pixel / Number grids imaged: 1 / Number real images: 9336 / Average exposure time: 3.0 sec. / Average electron dose: 74.9 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 1339334 |
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Startup model | Type of model: OTHER / Details: Ab initio |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.2) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.2) |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.3.2) / Number images used: 91042 |
-Atomic model buiding 1
Initial model |
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Software | Name: Coot (ver. 0.9.8.1) | ||||||||||||
Refinement | Space: REAL / Protocol: FLEXIBLE FIT | ||||||||||||
Output model | PDB-9asb: |