|Entry||Database: PDB / ID: 6mu2|
|Title||Structure of full-length IP3R1 channel in the Apo-state|
|Components||Inositol 1,4,5-trisphosphate receptor type 1|
|Keywords||MEMBRANE PROTEIN / inositol 1 / 4 / 5-trisphosphate receptor / calcium release channel / neuronal type 1|
|Function / homology|
Function and homology information
ion channel regulator activity involved in G protein-coupled receptor signaling pathway / Effects of PIP2 hydrolysis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / channel activator activity / inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels / Elevation of cytosolic Ca2+ levels / cGMP effects / smooth endoplasmic reticulum membrane / platelet dense tubular network / platelet dense granule membrane ...ion channel regulator activity involved in G protein-coupled receptor signaling pathway / Effects of PIP2 hydrolysis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / channel activator activity / inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels / Elevation of cytosolic Ca2+ levels / cGMP effects / smooth endoplasmic reticulum membrane / platelet dense tubular network / platelet dense granule membrane / negative regulation of calcium-mediated signaling / inositol phosphate-mediated signaling / inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity / calcineurin complex / epithelial fluid transport / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / voluntary musculoskeletal movement / inositol 1,4,5 trisphosphate binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / endoplasmic reticulum calcium ion homeostasis / positive regulation of calcium ion transport / positive regulation of hepatocyte proliferation / nuclear inner membrane / transport vesicle membrane / calcium channel regulator activity / Ion homeostasis / calcium-release channel activity / dendrite development / ligand-gated ion channel signaling pathway / ion channel modulating, G protein-coupled receptor signaling pathway / GABA-ergic synapse / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / release of sequestered calcium ion into cytosol / calcium channel inhibitor activity / phosphatidylinositol binding / liver regeneration / post-embryonic development / secretory granule membrane / sarcoplasmic reticulum / synaptic membrane / cellular response to cAMP / positive regulation of neuron projection development / Schaffer collateral - CA1 synapse / calcium-mediated signaling / negative regulation of neuron death / positive regulation of insulin secretion / cell morphogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / calcium ion transport / presynapse / nuclear envelope / cellular response to hypoxia / postsynapse / positive regulation of cytosolic calcium ion concentration / transmembrane transporter binding / protein phosphatase binding / response to hypoxia / postsynaptic density / positive regulation of apoptotic process / protein domain specific binding / membrane raft / intracellular membrane-bounded organelle / synapse / neuronal cell body / dendrite / protein-containing complex binding / endoplasmic reticulum membrane / nucleolus / perinuclear region of cytoplasm / endoplasmic reticulum / protein-containing complex / membrane / identical protein binding / 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 superfamily / MIR domain / MIR domain profile. / Domain in ryanodine and inositol trisphosphate receptors and protein O-mannosyltransferases / Ion transport domain / Ion transport protein / Armadillo-type fold
Similarity search - Domain/homology
Inositol 1,4,5-trisphosphate receptor type 1
Similarity search - Component
|Biological species||Rattus norvegicus (Norway rat)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å|
|Authors||Serysheva, I.I. / Fan, G. / Baker, M.R. / Wang, Z. / Seryshev, A. / Ludtke, S.J. / Baker, M.L.|
|Funding support|| United States, 6items |
|Citation||Journal: Cell Res / Year: 2018|
Title: Cryo-EM reveals ligand induced allostery underlying InsPR channel gating.
Authors: Guizhen Fan / Mariah R Baker / Zhao Wang / Alexander B Seryshev / Steven J Ludtke / Matthew L Baker / Irina I Serysheva /
Abstract: Inositol-1,4,5-trisphosphate receptors (InsPRs) are cation channels that mobilize Ca from intracellular stores in response to a wide range of cellular stimuli. The paradigm of InsPR activation is the ...Inositol-1,4,5-trisphosphate receptors (InsPRs) are cation channels that mobilize Ca from intracellular stores in response to a wide range of cellular stimuli. The paradigm of InsPR activation is the coupled interplay between binding of InsP and Ca that switches the ion conduction pathway between closed and open states to enable the passage of Ca through the channel. However, the molecular mechanism of how the receptor senses and decodes ligand-binding signals into gating motion remains unknown. Here, we present the electron cryo-microscopy structure of InsPR1 from rat cerebellum determined to 4.1 Å resolution in the presence of activating concentrations of Ca and adenophostin A (AdA), a structural mimetic of InsP and the most potent known agonist of the channel. Comparison with the 3.9 Å-resolution structure of InsPR1 in the Apo-state, also reported herein, reveals the binding arrangement of AdA in the tetrameric channel assembly and striking ligand-induced conformational rearrangements within cytoplasmic domains coupled to the dilation of a hydrophobic constriction at the gate. Together, our results provide critical insights into the mechanistic principles by which ligand-binding allosterically gates InsPR channel.
|Structure viewer||Molecule: |
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|PDBx/mmCIF format||6mu2.cif.gz||1.3 MB||Display||PDBx/mmCIF format|
|PDB format||pdb6mu2.ent.gz||990.3 KB||Display||PDB format|
|PDBx/mmJSON format||6mu2.json.gz||Tree view||PDBx/mmJSON format|
|Summary document||6mu2_validation.pdf.gz||909.3 KB||Display||wwPDB validaton report|
|Full document||6mu2_full_validation.pdf.gz||1.3 MB||Display|
|Data in XML||6mu2_validation.xml.gz||254.4 KB||Display|
|Data in CIF||6mu2_validation.cif.gz||379.2 KB||Display|
-Related structure data
|Related structure data|
M: map data used to model this data
C: citing same article (ref.)
|Similar structure data|
|PDB pages||PDBj / wwPDB / NCBI|
|Related items in Molecule of the Month|
B: Inositol 1,4,5-trisphosphate receptor type 1
A: Inositol 1,4,5-trisphosphate receptor type 1
D: Inositol 1,4,5-trisphosphate receptor type 1
C: Inositol 1,4,5-trisphosphate receptor type 1
Mass: 313657.406 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Rattus norvegicus (Norway rat) / Organ: Brain / Tissue: cerebellum / References: UniProt: P29994
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction|
|Component||Name: Inositol 1,4,5-trisphosphate receptor / Type: COMPLEX / Details: tetrameric assembly / Entity ID: all / Source: NATURAL|
|Molecular weight||Value: 1.3 MDa / Experimental value: NO|
|Source (natural)||Organism: Rattus norvegicus (Norway rat) / Cellular location: membrane / Organ: Brain / Organelle: endoplasmic reticulum / Tissue: Cerebellum|
|Buffer solution||pH: 7.4 |
Details: 50 mM Tris-HCl buffer (pH 7.4), 150 mM NaCl, 1 mM DTT, 0.4% CHAPS, 2 mM EGTA, 1 mM EDTA, protease inhibitors
|Specimen||Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Monodisperse sample|
|Specimen support||Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R2/1|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293 K|
-Electron microscopy imaging
Model: Tecnai F30 / Image courtesy: FEI Company
|Microscopy||Model: FEI TECNAI F30|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy|
|Specimen holder||Cryogen: NITROGEN|
Specimen holder model: GATAN 910 MULTI-SPECIMEN SINGLE TILT CRYO TRANSFER HOLDER
Temperature (max): 93 K / Temperature (min): 93 K
|Image recording||Average exposure time: 0.2 sec. / Electron dose: 1.3 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 9823|
|Image scans||Movie frames/image: 30 / Used frames/image: 2-17|
|CTF correction||Type: PHASE FLIPPING ONLY|
|Particle selection||Num. of particles selected: 207914|
|Symmetry||Point symmetry: C4 (4 fold cyclic)|
|3D reconstruction||Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 65438 |
Details: Image processing was performed independently using RELION and EMAN2 to near-atomic resolution in large regions of the structure. Local resolution assessment performed independently for each ...Details: Image processing was performed independently using RELION and EMAN2 to near-atomic resolution in large regions of the structure. Local resolution assessment performed independently for each map revealed different domains were better resolved by each software package. To avoid human bias and extract the most information from each reconstruction the final map was a locally filtered average of the EMAN2 and RELION map. To combine the two maps, a local resolution filter, based on a windowed FSC local resolution assessment, was performed independently on the two maps. The two locally filtered maps were then averaged together. The local filtration determines the contribution of each map at each resolution in each region of the final composite map, permitting each map to dominate in regions where better self-consistency was obtained during refinement.
Symmetry type: POINT
|Atomic model building||Protocol: AB INITIO MODEL / Space: REAL|
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