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Yorodumi- EMDB-33786: Cryo-EM structure of the imetit-bound histamine H4 receptor and G... -
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Basic information
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| Title | Cryo-EM structure of the imetit-bound histamine H4 receptor and Gq complex | |||||||||
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Keywords | GPCR / Aminergic receptor / Histamine receptor / MEMBRANE PROTEIN | |||||||||
| Function / homology | Function and homology informationHistamine receptors / histamine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / neurotransmitter receptor activity / regulation of MAPK cascade / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors ...Histamine receptors / histamine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / neurotransmitter receptor activity / regulation of MAPK cascade / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / positive regulation of cytosolic calcium ion concentration / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / chemical synaptic transmission / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / inflammatory response / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Im D / Iwata S / Asada H | |||||||||
| Funding support | Japan, 1 items
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Citation | Journal: Nat Commun / Year: 2023Title: Structural insights into the agonists binding and receptor selectivity of human histamine H receptor. Authors: Dohyun Im / Jun-Ichi Kishikawa / Yuki Shiimura / Hiromi Hisano / Akane Ito / Yoko Fujita-Fujiharu / Yukihiko Sugita / Takeshi Noda / Takayuki Kato / Hidetsugu Asada / So Iwata / ![]() Abstract: Histamine is a biogenic amine that participates in allergic and inflammatory processes by stimulating histamine receptors. The histamine H receptor (HR) is a potential therapeutic target for chronic ...Histamine is a biogenic amine that participates in allergic and inflammatory processes by stimulating histamine receptors. The histamine H receptor (HR) is a potential therapeutic target for chronic inflammatory diseases such as asthma and atopic dermatitis. Here, we show the cryo-electron microscopy structures of the HR-G complex bound with an endogenous agonist histamine or the selective agonist imetit bound in the orthosteric binding pocket. The structures demonstrate binding mode of histamine agonists and that the subtype-selective agonist binding causes conformational changes in Phe344, which, in turn, form the "aromatic slot". The results provide insights into the molecular underpinnings of the agonism of HR and subtype selectivity of histamine receptors, and show that the HR structures may be valuable in rational drug design of drugs targeting the HR. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_33786.map.gz | 112.4 MB | EMDB map data format | |
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| Header (meta data) | emd-33786-v30.xml emd-33786.xml | 23.8 KB 23.8 KB | Display Display | EMDB header |
| Images | emd_33786.png | 427.9 KB | ||
| Filedesc metadata | emd-33786.cif.gz | 7 KB | ||
| Others | emd_33786_half_map_1.map.gz emd_33786_half_map_2.map.gz | 116.2 MB 116.2 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33786 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33786 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7yfdMC ![]() 7yfcC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_33786.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.88 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #2
| File | emd_33786_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #1
| File | emd_33786_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
+Entire : Imetit bound histamine h4 receptor in complex with Gq
+Supramolecule #1: Imetit bound histamine h4 receptor in complex with Gq
+Supramolecule #2: Engineered G-alpha-q
+Supramolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #4: scFv16
+Supramolecule #5: Histamine H4 receptor
+Supramolecule #6: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #7: Nb35
+Macromolecule #1: Engineered G-alpha-q
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: scFv16
+Macromolecule #4: Histamine H4 receptor
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #6: Nb35
+Macromolecule #7: 2-(1~{H}-imidazol-5-yl)ethyl carbamimidothioate
+Macromolecule #8: CHOLESTEROL
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 10 mg/mL |
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| Buffer | pH: 7 |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 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: 2.0 µm / Nominal defocus min: 0.8 µm |
| Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
| Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 628467 |
| Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
| Final angle assignment | Type: MAXIMUM LIKELIHOOD |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
Japan, 1 items
Citation























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Y (Row.)
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FIELD EMISSION GUN

