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- PDB-8x5y: CryoEM structure of the histamine H1 receptor-BRIL/Anti BRIL Fab ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8x5y | ||||||
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Title | CryoEM structure of the histamine H1 receptor-BRIL/Anti BRIL Fab complex with astemizole | ||||||
![]() | Histamine H1 receptor,Soluble cytochrome b562 | ||||||
![]() | MEMBRANE PROTEIN / GPCR | ||||||
Function / homology | ![]() Histamine receptors / histamine receptor activity / cellular response to histamine / regulation of vascular permeability / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of vasoconstriction / electron transport chain / visual learning ...Histamine receptors / histamine receptor activity / cellular response to histamine / regulation of vascular permeability / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of vasoconstriction / electron transport chain / visual learning / regulation of synaptic plasticity / memory / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / chemical synaptic transmission / periplasmic space / electron transfer activity / inflammatory response / iron ion binding / G protein-coupled receptor signaling pathway / synapse / dendrite / heme binding / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
![]() | Wang, D.D. / Guo, Q. / Tao, Y.Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular mechanism of antihistamines recognition and regulation of the histamine H receptor. Authors: Dandan Wang / Qiong Guo / Zhangsong Wu / Ming Li / Binbin He / Yang Du / Kaiming Zhang / Yuyong Tao / ![]() Abstract: Histamine receptors are a group of G protein-coupled receptors (GPCRs) that play important roles in various physiological and pathophysiological conditions. Antihistamines that target the histamine H ...Histamine receptors are a group of G protein-coupled receptors (GPCRs) that play important roles in various physiological and pathophysiological conditions. Antihistamines that target the histamine H receptor (HR) have been widely used to relieve the symptoms of allergy and inflammation. Here, to uncover the details of the regulation of HR by the known second-generation antihistamines, thereby providing clues for the rational design of newer antihistamines, we determine the cryo-EM structure of HR in the apo form and bound to different antihistamines. In addition to the deep hydrophobic cavity, we identify a secondary ligand-binding site in HR, which potentially may support the introduction of new derivative groups to generate newer antihistamines. Furthermore, these structures show that antihistamines exert inverse regulation by utilizing a shared phenyl group that inserts into the deep cavity and block the movement of the toggle switch residue W428. Together, these results enrich our understanding of GPCR modulation and facilitate the structure-based design of novel antihistamines. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 67.6 KB | Display | ![]() |
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PDB format | ![]() | 46.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 38075MC ![]() 8x5xC ![]() 8x63C ![]() 8x64C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 50629.363 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: HRH1, cybC / Production host: ![]() ![]() |
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#2: Chemical | ChemComp-XB7 / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: CryoEM structure of the histamine H1 receptor-BRIL/Anti BRIL Fab complex with astemizole Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||
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Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | ||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Vitrification | Cryogen name: NITROGEN |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 357476 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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