[English] 日本語
Yorodumi
- EMDB-30996: Structural insights into the activation of human calcium-sensing ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-30996
TitleStructural insights into the activation of human calcium-sensing receptor
Map data
Sample
  • Complex: CaSR, TNCA, Ca, PO4
    • Protein or peptide: Extracellular calcium-sensing receptor
  • Ligand: PHOSPHATE ION
  • Ligand: CALCIUM ION
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CYCLOMETHYLTRYPTOPHAN
KeywordsG-protein-coupled receptor (GPCR) / Calcium-sensing receptor (CaSR) / cryo-electron microscopy (cryo-EM) / calcium ions / nanobody / STRUCTURAL PROTEIN
Function / homology
Function and homology information


bile acid secretion / regulation of presynaptic membrane potential / chemosensory behavior / response to fibroblast growth factor / cellular response to peptide / 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 ...bile acid secretion / regulation of presynaptic membrane potential / chemosensory behavior / response to fibroblast growth factor / cellular response to peptide / 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 / JNK cascade / positive regulation of vasoconstriction / axon terminus / chloride transmembrane transport / ossification / response to ischemia / G protein-coupled receptor activity / cellular response to glucose stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of insulin secretion / intracellular calcium ion homeostasis / vasodilation / integrin binding / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / basolateral plasma membrane / G alpha (q) signalling events / cellular response to hypoxia / 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
GPCR, family 3, extracellular calcium-sensing receptor-related / G-protein coupled receptors family 3 signature 1. / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / G-protein coupled receptors family 3 signature 3. / GPCR, family 3 / G-protein coupled receptors family 3 profile. ...GPCR, family 3, extracellular calcium-sensing receptor-related / G-protein coupled receptors family 3 signature 1. / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / G-protein coupled receptors family 3 signature 3. / GPCR, family 3 / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I
Similarity search - Domain/homology
Extracellular calcium-sensing receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsGeng Y / Chen XC
Funding support China, 2 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)No. 31670743 China
Chinese Academy of Sciences2015123456005 China
CitationJournal: Elife / Year: 2021
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
DepositionFeb 24, 2021-
Header (metadata) releaseSep 22, 2021-
Map releaseSep 22, 2021-
UpdateNov 20, 2024-
Current statusNov 20, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.538
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.538
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7e6t
  • Surface level: 0.538
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-7e6t
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_30996.png

Downloads & links

-
Map

FileDownload / File: emd_30996.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.11 Å/pix.
x 320 pix.
= 353.6 Å		1.11 Å/pix.
x 320 pix.
= 353.6 Å		1.11 Å/pix.
x 320 pix.
= 353.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.105 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.538 / Movie #1: 0.538
Minimum - Maximum-3.3517454 - 6.1665196
Average (Standard dev.)0.00036725172 (±0.09831477)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 353.6 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.1051.1051.105
M x/y/z320320320
origin x/y/z0.0000.0000.000
length x/y/z353.600353.600353.600
α/β/γ90.00090.00090.000
start NX/NY/NZ-140-140-140
NX/NY/NZ280280280
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS320320320
D min/max/mean-3.3526.1670.000

-
Supplemental data

-
Sample components

-
Entire : CaSR, TNCA, Ca, PO4

EntireName: CaSR, TNCA, Ca, PO4
Components
  • Complex: CaSR, TNCA, Ca, PO4
    • Protein or peptide: Extracellular calcium-sensing receptor
  • Ligand: PHOSPHATE ION
  • Ligand: CALCIUM ION
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CYCLOMETHYLTRYPTOPHAN

-
Supramolecule #1: CaSR, TNCA, Ca, PO4

SupramoleculeName: CaSR, TNCA, Ca, PO4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Extracellular calcium-sensing receptor

MacromoleculeName: Extracellular calcium-sensing receptor / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 97.326094 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

MacromoleculeName: PHOSPHATE ION / type: ligand / ID: 2 / Number of copies: 2 / Formula: PO4
Molecular weightTheoretical: 94.971 Da
Chemical component information

ChemComp-PO4:
PHOSPHATE ION

-
Macromolecule #3: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 6 / Formula: CA
Molecular weightTheoretical: 40.078 Da

-
Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 4 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

-
Macromolecule #5: CYCLOMETHYLTRYPTOPHAN

MacromoleculeName: CYCLOMETHYLTRYPTOPHAN / type: ligand / ID: 5 / Number of copies: 2 / Formula: TCR
Molecular weightTheoretical: 216.236 Da
Chemical component information

ChemComp-TCR:
CYCLOMETHYLTRYPTOPHAN

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation state2D array

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: NITROGEN

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsPhase plate: ZERNIKE PHASE PLATE
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 70.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD
Sample stageSpecimen holder model: SIDE ENTRY, EUCENTRIC / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 248900
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: PROJECTION MATCHING

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more