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Yorodumi- EMDB-25668: IP3 and ATP bound type 3 IP3 receptor in the pre-active B state -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25668 | ||||||||||||
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Title | IP3 and ATP bound type 3 IP3 receptor in the pre-active B state | ||||||||||||
Map data | Full sharpaned map (B=-100) | ||||||||||||
Sample |
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Function / homology | Function and homology information sensory perception of bitter taste / DAG and IP3 signaling / 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 / Elevation of cytosolic Ca2+ levels / Effects of PIP2 hydrolysis / PLC beta mediated events ...sensory perception of bitter taste / DAG and IP3 signaling / 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 / Elevation of cytosolic Ca2+ levels / Effects of PIP2 hydrolysis / PLC beta mediated events / inositol hexakisphosphate binding / inositol 1,4,5 trisphosphate binding / nuclear outer membrane / CLEC7A (Dectin-1) induces NFAT activation / cytoplasmic side of endoplasmic reticulum membrane / intracellularly gated calcium channel activity / brush border / Role of phospholipids in phagocytosis / calcium ion homeostasis / release of sequestered calcium ion into cytosol / Ion homeostasis / FCERI mediated Ca+2 mobilization / phosphatidylinositol binding / FCGR3A-mediated IL10 synthesis / secretory granule membrane / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / VEGFR2 mediated cell proliferation / sarcoplasmic reticulum / Regulation of insulin secretion / long-term synaptic potentiation / response to calcium ion / memory / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / sensory perception of taste / apical part of cell / myelin sheath / Ca2+ pathway / positive regulation of cytosolic calcium ion concentration / 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 | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
Authors | Schmitz EA / Takahashi H / Karakas E | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: 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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_25668.map.gz | 216.7 MB | EMDB map data format | |
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Header (meta data) | emd-25668-v30.xml emd-25668.xml | 26.6 KB 26.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_25668_fsc.xml | 18 KB | Display | FSC data file |
Images | emd_25668.png | 71.6 KB | ||
Others | emd_25668_additional_1.map.gz emd_25668_additional_2.map.gz emd_25668_half_map_1.map.gz emd_25668_half_map_2.map.gz | 379.6 MB 208.8 MB 391.3 MB 391.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25668 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25668 | HTTPS FTP |
-Validation report
Summary document | emd_25668_validation.pdf.gz | 845.9 KB | Display | EMDB validaton report |
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Full document | emd_25668_full_validation.pdf.gz | 845.4 KB | Display | |
Data in XML | emd_25668_validation.xml.gz | 24.9 KB | Display | |
Data in CIF | emd_25668_validation.cif.gz | 32.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25668 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25668 | HTTPS FTP |
-Related structure data
Related structure data | 7t3qMC 7t3pC 7t3rC 7t3tC 7t3uC M: atomic model generated by this map C: citing same article (ref.) |
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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_25668.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Full sharpaned map (B=-100) | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.828 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Composite map creating by local maps.
File | emd_25668_additional_1.map | ||||||||||||
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Annotation | Composite map creating by local maps. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Full unsharpened map
File | emd_25668_additional_2.map | ||||||||||||
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Annotation | Full unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: IP3 and ATP bound type 3 IP3 receptor in the pre-active B state
File | emd_25668_half_map_1.map | ||||||||||||
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Annotation | IP3 and ATP bound type 3 IP3 receptor in the pre-active B state | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: IP3 and ATP bound type 3 IP3 receptor in the pre-active B state
File | emd_25668_half_map_2.map | ||||||||||||
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Annotation | IP3 and ATP bound type 3 IP3 receptor in the pre-active B state | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Inositol 1,4,5-trisphosphate receptor type 3
Entire | Name: Inositol 1,4,5-trisphosphate receptor type 3 |
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Components |
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-Supramolecule #1: Inositol 1,4,5-trisphosphate receptor type 3
Supramolecule | Name: Inositol 1,4,5-trisphosphate receptor type 3 / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Molecular weight | Theoretical: 1.2 MDa |
-Macromolecule #1: Inositol 1,4,5-trisphosphate receptor type 3
Macromolecule | Name: Inositol 1,4,5-trisphosphate receptor type 3 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 299.325875 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: 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) |
-Macromolecule #2: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 2 / Number of copies: 4 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #3: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE
Macromolecule | Name: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 4 / Formula: I3P |
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Molecular weight | Theoretical: 420.096 Da |
Chemical component information | ChemComp-I3P: |
-Macromolecule #4: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 4 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ChemComp-ATP: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.8 mg/mL | ||||||||||||||||||||||||||||||
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Buffer | pH: 8 Component:
Details: IP3, ATP, and CaCl2 were added before cryo-grid preparation. | ||||||||||||||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film 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 beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination 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 |