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Yorodumi- PDB-8ibu: Cryo-EM structure of the erythromycin-bound motilin receptor-Gq p... -
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-Basic information
Entry | Database: PDB / ID: 8ibu | ||||||
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Title | Cryo-EM structure of the erythromycin-bound motilin receptor-Gq protein complex | ||||||
Components |
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Keywords | SIGNALING PROTEIN / Cryo-EM / GPCR / erythromycin / motilin receptor / Gq / complex | ||||||
Function / homology | Function and homology information hormone binding / G protein-coupled peptide receptor activity / Peptide ligand-binding receptors / electron transport chain / 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 activation ...hormone binding / G protein-coupled peptide receptor activity / Peptide ligand-binding receptors / electron transport chain / 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 activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / iron ion binding / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / heme binding / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Escherichia coli (E. coli) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.51 Å | ||||||
Authors | You, C. / Jiang, Y. / Xu, H.E. / Xu, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Sci Adv / Year: 2023 Title: Structural basis for motilin and erythromycin recognition by motilin receptor. Authors: Chongzhao You / Yumu Zhang / Youwei Xu / Peiyu Xu / Zhen Li / Huadong Li / Sijie Huang / Zecai Chen / Jingru Li / H Eric Xu / Yi Jiang / Abstract: Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), ...Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macrolide antibiotics, such as erythromycin. It has attracted extensive attention as a potential drug target for GI disorders. We report two structures of G-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ibu.cif.gz | 224.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ibu.ent.gz | 169 KB | Display | PDB format |
PDBx/mmJSON format | 8ibu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ibu_validation.pdf.gz | 516.9 KB | Display | wwPDB validaton report |
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Full document | 8ibu_full_validation.pdf.gz | 537.3 KB | Display | |
Data in XML | 8ibu_validation.xml.gz | 25 KB | Display | |
Data in CIF | 8ibu_validation.cif.gz | 37.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ib/8ibu ftp://data.pdbj.org/pub/pdb/validation_reports/ib/8ibu | HTTPS FTP |
-Related structure data
Related structure data | 35345MC 8ibvC 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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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 41724.383 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper) |
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#2: Protein | Mass: 40226.992 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873 |
#4: Protein | Mass: 7729.947 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules ER
#3: Antibody | Mass: 26277.299 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper) |
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#5: Protein | Mass: 81667.000 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human) Gene: cybC, MLNR, GPR38, MTLR, MTLR1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P0ABE7, UniProt: O43193 |
#6: Chemical | ChemComp-ERY / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Erythromycin-bound motilin receptor-Gq protein complex Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 20000 nm / Nominal defocus min: 8000 nm |
Image recording | Electron dose: 1.91 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.51 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 261108 / Symmetry type: POINT |