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- EMDB-7986: Class 4 IP3-bound human type 3 1,4,5-inositol trisphosphate receptor -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7986 | |||||||||
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Title | Class 4 IP3-bound human type 3 1,4,5-inositol trisphosphate receptor | |||||||||
![]() | Class 4 IP3-bound human type 3 1,4,5-inositol trisphosphate receptor | |||||||||
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Function / homology | ![]() 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 / memory / Sensory perception of sweet, bitter, and umami (glutamate) taste / response to calcium ion / 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 | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.01 Å | |||||||||
![]() | Hite RK / Paknejad N | |||||||||
![]() | ![]() Title: Structural basis for the regulation of inositol trisphosphate receptors by Ca and IP. Authors: Navid Paknejad / Richard K Hite / ![]() Abstract: Inositol trisphosphate receptors (IPRs) are ubiquitous Ca-permeable channels that mediate release of Ca from the endoplasmic reticulum, thereby regulating numerous processes including cell division, ...Inositol trisphosphate receptors (IPRs) are ubiquitous Ca-permeable channels that mediate release of Ca from the endoplasmic reticulum, thereby regulating numerous processes including cell division, cell death, differentiation and fertilization. IPRs are jointly activated by inositol trisphosphate (IP) and their permeant ion, Ca. At high concentrations, however, Ca inhibits activity, ensuring precise spatiotemporal control over intracellular Ca. Despite extensive characterization of IPR, the mechanisms through which these molecules control channel gating have remained elusive. Here, we present structures of full-length human type 3 IPRs in ligand-bound and ligand-free states. Multiple IP-bound structures demonstrate that the large cytoplasmic domain provides a platform for propagation of long-range conformational changes to the ion-conduction gate. Structures in the presence of Ca reveal two Ca-binding sites that induce the disruption of numerous interactions between subunits, thereby inhibiting IPR. These structures thus provide a mechanistic basis for beginning to understand the regulation of IPR. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 200.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.5 KB 18.5 KB | Display Display | ![]() |
Images | ![]() | 137 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6dqzMC ![]() 7978C ![]() 7979C ![]() 7980C ![]() 7981C ![]() 7982C ![]() 7983C ![]() 7984C ![]() 7985C ![]() 7987C ![]() 7988C ![]() 7989C ![]() 7990C ![]() 7991C ![]() 7992C ![]() 7993C ![]() 7994C ![]() 7995C ![]() 7996C ![]() 6dqjC ![]() 6dqnC ![]() 6dqsC ![]() 6dqvC ![]() 6dr0C ![]() 6dr2C ![]() 6draC ![]() 6drcC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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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 | Class 4 IP3-bound human type 3 1,4,5-inositol trisphosphate receptor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.088 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : human type 3 inositol 1,4,5-trisphosphate receptor
Entire | Name: human type 3 inositol 1,4,5-trisphosphate receptor |
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Components |
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-Supramolecule #1: human type 3 inositol 1,4,5-trisphosphate receptor
Supramolecule | Name: human type 3 inositol 1,4,5-trisphosphate receptor / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-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: ![]() |
Molecular weight | Theoretical: 304.488688 KDa |
Recombinant expression | Organism: ![]() |
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 SLVSNEGEGE QNEIRILQDK LNSTMKLVSH LT AQLNELK EQMTEQRKRR QRLGFVDVQN CISR |
-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: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 8 mg/mL | |||||||||||||||||||||
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Buffer | pH: 8 Component:
Details: 150mM Nacl 50mM Tris-HCl, pH 8.0 2mM DTT 0.06% Digitonin 5mM EGTA 50 micromolar IP3 | |||||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY | |||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV / Details: Blot for 2 seconds prior to freezing. | |||||||||||||||||||||
Details | ligand-free human type 3 inositol 1,4,5-trisphosphate receptor in detergent micelles |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 7420 pixel / Digitization - Dimensions - Height: 7676 pixel / Digitization - Sampling interval: 5.0 µm / Digitization - Frames/image: 1-40 / Number grids imaged: 1 / Number real images: 4519 / Average exposure time: 8.0 sec. / Average electron dose: 61.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus min: 1.0 µm / Nominal magnification: 22500 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 376.7 / Target criteria: map-to-model FSC |
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Output model | ![]() PDB-6dqz: |