[English] 日本語
Yorodumi
- EMDB-25671: IP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-25671
TitleIP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state
Map datasharpened map (B=-100)
Sample
  • Complex: Inositol 1,4,5-trisphosphate receptor type 3
    • Protein or peptide: Inositol 1,4,5-trisphosphate receptor type 3
  • Ligand: ZINC ION
  • Ligand: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE
  • Ligand: ADENOSINE-5'-TRIPHOSPHATE
  • Ligand: CALCIUM ION
KeywordsIP3 receptor / calcium signaling / METAL TRANSPORT
Function / homology
Function and homology information


DAG and IP3 signaling / sensory perception of bitter taste / inositol 1,3,4,5 tetrakisphosphate binding / sensory perception of umami taste / inositol 1,4,5-trisphosphate-gated calcium channel activity / sensory perception of sweet taste / platelet dense tubular network membrane / Effects of PIP2 hydrolysis / Elevation of cytosolic Ca2+ levels / PLC beta mediated events ...DAG and IP3 signaling / sensory perception of bitter taste / inositol 1,3,4,5 tetrakisphosphate binding / sensory perception of umami taste / inositol 1,4,5-trisphosphate-gated calcium channel activity / sensory perception of sweet taste / platelet dense tubular network membrane / Effects of PIP2 hydrolysis / Elevation of cytosolic Ca2+ levels / PLC beta mediated events / inositol 1,4,5 trisphosphate binding / nuclear outer membrane / inositol hexakisphosphate binding / CLEC7A (Dectin-1) induces NFAT activation / transport vesicle membrane / cytoplasmic side of endoplasmic reticulum membrane / intracellularly gated calcium channel activity / brush border / Role of phospholipids in phagocytosis / calcium ion homeostasis / Ion homeostasis / release of sequestered calcium ion into cytosol / FCERI mediated Ca+2 mobilization / phosphatidylinositol binding / FCGR3A-mediated IL10 synthesis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / secretory granule membrane / VEGFR2 mediated cell proliferation / sarcoplasmic reticulum / Regulation of insulin secretion / long-term synaptic potentiation / platelet activation / memory / response to calcium ion / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / apical part of cell / sensory perception of taste / positive regulation of cytosolic calcium ion concentration / Ca2+ pathway / protein homotetramerization / receptor complex / G protein-coupled receptor signaling pathway / neuronal cell body / calcium ion binding / endoplasmic reticulum membrane / nucleolus / endoplasmic reticulum / nucleoplasm / membrane / plasma membrane / cytoplasm
Similarity search - Function
Inositol 1,4,5-trisphosphate receptor / RyR/IP3 receptor binding core, RIH domain superfamily / RyR/IP3R Homology associated domain / Inositol 1,4,5-trisphosphate/ryanodine receptor / RIH domain / RyR and IP3R Homology associated / Inositol 1,4,5-trisphosphate/ryanodine receptor / RIH domain / : / MIR motif ...Inositol 1,4,5-trisphosphate receptor / RyR/IP3 receptor binding core, RIH domain superfamily / RyR/IP3R Homology associated domain / Inositol 1,4,5-trisphosphate/ryanodine receptor / RIH domain / RyR and IP3R Homology associated / Inositol 1,4,5-trisphosphate/ryanodine receptor / RIH domain / : / MIR motif / MIR domain / MIR domain profile. / Domain in ryanodine and inositol trisphosphate receptors and protein O-mannosyltransferases / Mir domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsSchmitz EA / Takahashi H
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM141251 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)P30DK020593 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)T32GM008320 United States
CitationJournal: Nat Commun / Year: 2022
Title: Structural basis for activation and gating of IP receptors.
Authors: Emily A Schmitz / Hirohide Takahashi / Erkan Karakas /
Abstract: A pivotal component of the calcium (Ca) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP) receptor (IPR), which mediates Ca release from the endoplasmic reticulum (ER), controlling ...A pivotal component of the calcium (Ca) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP) receptor (IPR), which mediates Ca release from the endoplasmic reticulum (ER), controlling cytoplasmic and organellar Ca concentrations. IPRs are co-activated by IP and Ca, inhibited by Ca at high concentrations, and potentiated by ATP. However, the underlying molecular mechanisms are unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human type-3 IPR obtained from a single dataset in multiple gating conformations: IP-ATP bound pre-active states with closed channels, IP-ATP-Ca bound active state with an open channel, and IP-ATP-Ca bound inactive state with a closed channel. The structures demonstrate how IP-induced conformational changes prime the receptor for activation by Ca, how Ca binding leads to channel opening, and how ATP modulates the activity, providing insights into the long-sought questions regarding the molecular mechanism underpinning receptor activation and gating.
History
DepositionDec 8, 2021-
Header (metadata) releaseMar 23, 2022-
Map releaseMar 23, 2022-
UpdateNov 6, 2024-
Current statusNov 6, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_25671.png

Downloads & links

-
Map

FileDownload / File: emd_25671.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationsharpened map (B=-100)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 480 pix.
= 397.44 Å		0.83 Å/pix.
x 480 pix.
= 397.44 Å		0.83 Å/pix.
x 480 pix.
= 397.44 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.828 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-1.1708896 - 1.9105759
Average (Standard dev.)0.00068618136 (±0.03825987)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 397.44 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_25671_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: composite map generated using the local refinement maps

Fileemd_25671_additional_1.map
Annotationcomposite map generated using the local refinement maps
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: unsharpened main map

Fileemd_25671_additional_2.map
Annotationunsharpened main map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: IP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state

Fileemd_25671_half_map_1.map
AnnotationIP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: IP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state

Fileemd_25671_half_map_2.map
AnnotationIP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Inositol 1,4,5-trisphosphate receptor type 3

EntireName: Inositol 1,4,5-trisphosphate receptor type 3
Components
  • Complex: Inositol 1,4,5-trisphosphate receptor type 3
    • Protein or peptide: Inositol 1,4,5-trisphosphate receptor type 3
  • Ligand: ZINC ION
  • Ligand: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE
  • Ligand: ADENOSINE-5'-TRIPHOSPHATE
  • Ligand: CALCIUM ION

-
Supramolecule #1: Inositol 1,4,5-trisphosphate receptor type 3

SupramoleculeName: Inositol 1,4,5-trisphosphate receptor type 3 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 1.2 MDa

-
Macromolecule #1: Inositol 1,4,5-trisphosphate receptor type 3

MacromoleculeName: Inositol 1,4,5-trisphosphate receptor type 3 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 299.325875 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MSEMSSFLHI GDIVSLYAEG SVNGFISTLG LVDDRCVVEP AAGDLDNPPK KFRDCLFKVC PMNRYSAQKQ YWKAKQTKQD KEKIADVVL LQKLQHAAQM EQKQNDTENK KVHGDVVKYG SVIQLLHMKS NKYLTVNKRL PALLEKNAMR VTLDATGNEG S WLFIQPFW ...String:
MSEMSSFLHI GDIVSLYAEG SVNGFISTLG LVDDRCVVEP AAGDLDNPPK KFRDCLFKVC PMNRYSAQKQ YWKAKQTKQD KEKIADVVL LQKLQHAAQM EQKQNDTENK KVHGDVVKYG SVIQLLHMKS NKYLTVNKRL PALLEKNAMR VTLDATGNEG S WLFIQPFW KLRSNGDNVV VGDKVILNPV NAGQPLHASN YELSDNAGCK EVNSVNCNTS WKINLFMQFR DHLEEVLKGG DV VRLFHAE QEKFLTCDEY KGKLQVFLRT TLRQSATSAT SSNALWEVEV VHHDPCRGGA GHWNGLYRFK HLATGNYLAA EEN PSYKGD ASDPKAAGMG AQGRTGRRNA GEKIKYCLVA VPHGNDIASL FELDPTTLQK TDSFVPRNSY VRLRHLCTNT WIQS TNVPI DIEEERPIRL MLGTCPTKED KEAFAIVSVP VSEIRDLDFA NDASSMLASA VEKLNEGFIS QNDRRFVIQL LEDLV FFVS DVPNNGQNVL DIMVTKPNRE RQKLMREQNI LKQVFGILKA PFREKGGEGP LVRLEELSDQ KNAPYQHMFR LCYRVL RHS QEDYRKNQEH IAKQFGMMQS QIGYDILAED TITALLHNNR KLLEKHITKT EVETFVSLVR KNREPRFLDY LSDLCVS NH IAIPVTQELI CKCVLDPKNS DILIRTELRP VKEMAQSHEY LSIEYSEEEV WLTWTDKNNE HHEKSVRQLA QEARAGNA H DENVLSYYRY QLKLFARMCL DRQYLAIDEI SQQLGVDLIF LCMADEMLPF DLRASFCHLM LHVHVDRDPQ ELVTPVKFA RLWTEIPTAI TIKDYDSNLN ASRDDKKNKF ANTMEFVEDY LNNVVSEAVP FANEEKNKLT FEVVSLAHNL IYFGFYSFSE LLRLTRTLL GIIDCVQGPP AMLQAYEDPG GKNVRRSIQG VGHMMSTMVL SRKQSVFSAP SLSAGASAAE PLDRSKFEEN E DIVVMETK LKILEILQFI LNVRLDYRIS YLLSVFKKEF VEVFPMQDSG ADGTAPAFDS TTANMNLDRI GEQAEAMFGV GK TSSMLEV DDEGGRMFLR VLIHLTMHDY APLVSGALQL LFKHFSQRQE AMHTFKQVQL LISAQDVENY KVIKSELDRL RTM VEKSEL WVDKKGSGKG EEVEAGAAKD KKERPTDEEG FLHPPGEKSS ENYQIVKGIL ERLNKMCGVG EQMRKKQQRL LKNM DAHKV MLDLLQIPYD KGDAKMMEIL RYTHQFLQKF CAGNPGNQAL LHKHLHLFLT PGLLEAETMQ HIFLNNYQLC SEISE PVLQ HFVHLLATHG RHVQYLDFLH TVIKAEGKYV KKCQDMIMTE LTNAGDDVVV FYNDKASLAH LLDMMKAARD GVEDHS PLM YHISLVDLLA ACAEGKNVYT EIKCTSLLPL EDVVSVVTHE DCITEVKMAY VNFVNHCYVD TEVEMKEIYT SNHIWTL FE NFTLDMARVC SKREKRVADP TLEKYVLSVV LDTINAFFSS PFSENSTSLQ THQTIVVQLL QSTTRLLECP WLQQQHKG S VEACIRTLAM VAKGRAILLP MDLDAHISSM LSSGASCAAA AQRNASSYKA TTRAFPRVTP TANQWDYKNI IEKLQDIIT ALEERLKPLV QAELSVLVDV LHWPELLFLE GSEAYQRCES GGFLSKLIQH TKDLMESEEK LCIKVLRTLQ QMLLKKTKYG DRGNQLRKM LLQNYLQNRK STSRGDLPDP IGTGLDPDWS AIAATQCRLD KEGATKLVCD LITSTKNEKI FQESIGLAIH L LDGGNTEI QKSFHNLMMS DKKSERFFKV LHDRMKRAQQ ETKSTVAVNM NDLGSQPHED REPVDPTTKG RVASFSIPGS SS RYSLGPS LRRGHEVSER VQSSEMGTSV LIMQPILRFL QLLCENHNRD LQNFLRCQNN KTNYNLVCET LQFLDIMCGS TTG GLGLLG LYINEDNVGL VIQTLETLTE YCQGPCHENQ TCIVTHESNG IDIITALILN DISPLCKYRM DLVLQLKDNA SKLL LALME SRHDSENAER ILISLRPQEL VDVIKKAYLQ EEERENSEVS PREVGHNIYI LALQLSRHNK QLQHLLKPVK RIQEE EAEG ISSMLSLNNK QLSQMLKSSA PAQEEEEDPL AYYENHTSQI EIVRQDRSME QIVFPVPGIC QFLTEETKHR LFTTTE QDE QGSKVSDFFD QSSFLHNEME WQRKLRSMPL IYWFSRRMTL WGSISFNLAV FINIIIAFFY PYMEGASTGV LDSPLIS LL FWILICFSIA ALFTKRYSIR PLIVALILRS IYYLGIGPTL NILGALNLTN KIVFVVSFVG NRGTFIRGYK AMVMDMEF L YHVGYILTSV LGLFAHELFY SILLFDLIYR EETLFNVIKS VTRNGRSILL TALLALILVY LFSIVGFLFL KDDFILEVD RLPNNHSTAS PLGMPHGAAA FVDTCSGDKM DCVSGLSVPE VLEEDRELDS TERACDTLLM CIVTVMNHGL RNGGGVGDIL RKPSKDESL FPARVVYDLL FFFIVIIIVL NLIFGVIIDT FADLRSEKQK KEEILKTTCF ICGLERDKFD NKTVSFEEHI K LEHNMWNY LYFIVLVRVK NKTDYTGPES YVAQMIKNKN LDWFPRMRAM SLV(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)

UniProtKB: Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3

-
Macromolecule #2: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 2 / Number of copies: 4 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

-
Macromolecule #3: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE

MacromoleculeName: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 2 / Formula: I3P
Molecular weightTheoretical: 420.096 Da
Chemical component information

ChemComp-I3P:
D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE

-
Macromolecule #4: ADENOSINE-5'-TRIPHOSPHATE

MacromoleculeName: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 4 / Formula: ATP
Molecular weightTheoretical: 507.181 Da
Chemical component information

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

-
Macromolecule #5: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 5 / Number of copies: 4 / Formula: CA
Molecular weightTheoretical: 40.078 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1.8 mg/mL
BufferpH: 8
Component:
ConcentrationFormulaName
0.2 MNaClSodium Chloride
0.02 MTris-HCl
1.0 mMEDTA
2.0 mMTCEP
0.005 %Lauryl neopentyl glycol
0.005 %glyco-diosgenin
5.0 mMATP
0.5 mMIP3inositol 1,4,5-triphosphate
0.1 mMCaCl2Calcium chloride

Details: IP3, ATP, and CaCl2 were added before cryo-grid preparation.
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 4 / Number real images: 42361 / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: EMDB MAP
EMDB ID:

20849

Final reconstructionNumber classes used: 2 / Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 198441
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationSoftware - Name: RELION
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

6uqk


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-7t3u:
IP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state

+
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