+Open data
-Basic information
Entry | Database: PDB / ID: 8tkd | ||||||||||||
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Title | Human Type 3 IP3 Receptor - Preactivated State (+IP3/ATP) | ||||||||||||
Components | Inositol 1,4,5-trisphosphate receptor type 3 | ||||||||||||
Keywords | TRANSPORT PROTEIN / Ion Channel / Calcium Channel / Endoplasmic Reticulum | ||||||||||||
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 / intracellularly gated calcium channel activity / cytoplasmic side of endoplasmic reticulum membrane / 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 / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||||||||
Authors | Paknejad, N. / Sapuru, V. / Hite, R.K. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural titration reveals Ca-dependent conformational landscape of the IP receptor. Authors: Navid Paknejad / Vinay Sapuru / Richard K Hite / Abstract: Inositol 1,4,5-trisphosphate receptors (IPRs) are endoplasmic reticulum Ca channels whose biphasic dependence on cytosolic Ca gives rise to Ca oscillations that regulate fertilization, cell division ...Inositol 1,4,5-trisphosphate receptors (IPRs) are endoplasmic reticulum Ca channels whose biphasic dependence on cytosolic Ca gives rise to Ca oscillations that regulate fertilization, cell division and cell death. Despite the critical roles of IPR-mediated Ca responses, the structural underpinnings of the biphasic Ca dependence that underlies Ca oscillations are incompletely understood. Here, we collect cryo-EM images of an IPR with Ca concentrations spanning five orders of magnitude. Unbiased image analysis reveals that Ca binding does not explicitly induce conformational changes but rather biases a complex conformational landscape consisting of resting, preactivated, activated, and inhibited states. Using particle counts as a proxy for relative conformational free energy, we demonstrate that Ca binding at a high-affinity site allows IPRs to activate by escaping a low-energy resting state through an ensemble of preactivated states. At high Ca concentrations, IPRs preferentially enter an inhibited state stabilized by a second, low-affinity Ca binding site. Together, these studies provide a mechanistic basis for the biphasic Ca-dependence of IPR channel activity. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8tkd.cif.gz | 3.5 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8tkd.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8tkd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8tkd_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8tkd_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8tkd_validation.xml.gz | 211.2 KB | Display | |
Data in CIF | 8tkd_validation.cif.gz | 321.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tk/8tkd ftp://data.pdbj.org/pub/pdb/validation_reports/tk/8tkd | HTTPS FTP |
-Related structure data
Related structure data | 41347MC 8tk8C 8tkeC 8tkfC 8tkgC 8tkhC 8tkiC 8tl9C 8tlaC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Ens-ID: ens_1
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