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- EMDB-43811: Structure of human calcium-sensing receptor in complex with chime... -
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Open data
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Basic information
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Title | Structure of human calcium-sensing receptor in complex with chimeric Gq (miniGisq) protein in nanodiscs | |||||||||
![]() | Human CaSR-miniGis complex in nanodiscs, composite map of locally refined CaSR ECD, CaSR TMD and G protein | |||||||||
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Function / homology | ![]() bile acid secretion / chemosensory behavior / cellular response to peptide / response to fibroblast growth factor / sensory perception of chemical stimulus / cellular response to vitamin D / mu-type opioid receptor binding / phosphatidylinositol phospholipase C activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | 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 | ![]()
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![]() | ![]() 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 | ![]() | 10.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 27.6 KB 27.6 KB | Display Display | ![]() |
Images | ![]() | 99.2 KB | ||
Filedesc metadata | ![]() | 8.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9asbMC ![]() 9avgC ![]() 9avlC ![]() 9axfC ![]() 9ayfC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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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
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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 | ![]() |
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Aggregation state | particle |
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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.. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
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 |
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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: ![]() | ||||||||||||
Refinement | Space: REAL / Protocol: FLEXIBLE FIT | ||||||||||||
Output model | ![]() PDB-9asb: |