[English] 日本語
Yorodumi
- PDB-7f83: Crystal Structure of a receptor in Complex with inverse agonist -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7f83
TitleCrystal Structure of a receptor in Complex with inverse agonist
ComponentsGrowth hormone secretagogue receptor type 1,Soluble cytochrome b562
KeywordsSIGNALING PROTEIN / GPCR / Ghrelin / Inverse agonist
Function / homology
Function and homology information


growth hormone secretagogue receptor activity / regulation of hindgut contraction / regulation of growth hormone secretion / growth hormone-releasing hormone receptor activity / positive regulation of small intestinal transit / negative regulation of locomotion involved in locomotory behavior / regulation of gastric motility / regulation of transmission of nerve impulse / response to follicle-stimulating hormone / growth hormone secretion ...growth hormone secretagogue receptor activity / regulation of hindgut contraction / regulation of growth hormone secretion / growth hormone-releasing hormone receptor activity / positive regulation of small intestinal transit / negative regulation of locomotion involved in locomotory behavior / regulation of gastric motility / regulation of transmission of nerve impulse / response to follicle-stimulating hormone / growth hormone secretion / ghrelin secretion / positive regulation of eating behavior / negative regulation of norepinephrine secretion / positive regulation of appetite / positive regulation of small intestine smooth muscle contraction / negative regulation of macrophage apoptotic process / adult feeding behavior / negative regulation of appetite / positive regulation of multicellular organism growth / actin polymerization or depolymerization / cellular response to thyroid hormone stimulus / response to growth hormone / positive regulation of insulin-like growth factor receptor signaling pathway / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / response to food / positive regulation of vascular endothelial cell proliferation / negative regulation of interleukin-1 beta production / cellular response to insulin-like growth factor stimulus / regulation of postsynapse organization / response to L-glutamate / regulation of synapse assembly / positive regulation of fatty acid metabolic process / postsynaptic modulation of chemical synaptic transmission / response to dexamethasone / positive regulation of sprouting angiogenesis / peptide hormone binding / negative regulation of interleukin-6 production / negative regulation of tumor necrosis factor production / decidualization / negative regulation of insulin secretion / hormone-mediated signaling pathway / Peptide ligand-binding receptors / insulin-like growth factor receptor signaling pathway / response to hormone / synaptic membrane / G protein-coupled receptor activity / electron transport chain / Schaffer collateral - CA1 synapse / negative regulation of inflammatory response / cellular response to insulin stimulus / response to estradiol / postsynapse / spermatogenesis / G alpha (q) signalling events / cellular response to lipopolysaccharide / periplasmic space / electron transfer activity / learning or memory / neuron projection / iron ion binding / membrane raft / G protein-coupled receptor signaling pathway / glutamatergic synapse / heme binding / cell surface / identical protein binding / plasma membrane
Similarity search - Function
Growth hormone secretagogue receptor/motilin receptor / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family)
Similarity search - Domain/homology
Chem-1KQ / (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / Soluble cytochrome b562 / Growth hormone secretagogue receptor type 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Escherichia coli (E. coli)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.94 Å
AuthorsXu, Z. / Shao, Z.
CitationJournal: Nat Commun / Year: 2022
Title: Molecular mechanism of agonism and inverse agonism in ghrelin receptor.
Authors: Jiao Qin / Ye Cai / Zheng Xu / Qianqian Ming / Su-Yu Ji / Chao Wu / Huibing Zhang / Chunyou Mao / Dan-Dan Shen / Kunio Hirata / Yanbin Ma / Wei Yan / Yan Zhang / Zhenhua Shao /
Abstract: Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are ...Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but the molecular mechanism of such ligands remains insufficiently understood. Here, we report a crystal structure of the ghrelin receptor bound to the inverse agonist PF-05190457 and a cryo-electron microscopy structure of the active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin. Our structures reveal a distinct binding mode of the inverse agonist PF-05190457 in the ghrelin receptor, different from the binding mode of agonists and neutral antagonists. Combining the structural comparisons and cellular function assays, we find that a polar network and a notable hydrophobic cluster are required for receptor activation and constitutive activity. Together, our study provides insights into the detailed mechanism of ghrelin receptor binding to agonists and inverse agonists, and paves the way to design specific ligands targeting ghrelin receptors.
History
DepositionJul 1, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 19, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 26, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Growth hormone secretagogue receptor type 1,Soluble cytochrome b562
B: Growth hormone secretagogue receptor type 1,Soluble cytochrome b562
hetero molecules


Theoretical massNumber of molelcules
Total (without water)97,53110
Polymers94,3662
Non-polymers3,1658
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2680 Å2
ΔGint-22 kcal/mol
Surface area40470 Å2
MethodPISA
Unit cell
Length a, b, c (Å)84.710, 58.680, 119.240
Angle α, β, γ (deg.)90.00, 90.60, 90.00
Int Tables number4
Space group name H-MP1211
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

-
Components

#1: Protein Growth hormone secretagogue receptor type 1,Soluble cytochrome b562 / GHS-R / GH-releasing peptide receptor / GHRP / Ghrelin receptor / Cytochrome b-562


Mass: 47183.223 Da / Num. of mol.: 2 / Mutation: T130K,N188Q,M1012W,H1107I,R1111L
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Escherichia coli (E. coli)
Gene: GHSR, cybC / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q92847, UniProt: P0ABE7
#2: Chemical
ChemComp-OLC / (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / 1-Oleoyl-R-glycerol


Mass: 356.540 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C21H40O4
#3: Chemical ChemComp-1KQ / 2-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)-1-[2-[(1R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone


Mass: 512.669 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H32N6OS
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.09 Å3/Da / Density % sol: 60.15 %
Crystal growTemperature: 293.15 K / Method: lipidic cubic phase / pH: 7
Details: 100mM HEPES, pH 7.0, 25%-36% PEG300, 80mM - 150mM NH4F

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL41XU / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Feb 7, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.94→39.78 Å / Num. obs: 25315 / % possible obs: 100 % / Redundancy: 24.53 % / Biso Wilson estimate: 81.38 Å2 / Rmerge(I) obs: 0.664 / Net I/σ(I): 10.37
Reflection shellResolution: 2.94→3.12 Å / Redundancy: 23.68 % / Rmerge(I) obs: 5.083 / Mean I/σ(I) obs: 1.31 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.19.2-4158refinement
XDSdata reduction
XSCALEdata scaling
PDB_EXTRACT3.27data extraction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6KO5

6ko5


Resolution: 2.94→39.78 Å / SU ML: 0.415 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 26.565
Stereochemistry target values: GEOSTD + MONOMER LIBRARY + CDL V1.2
RfactorNum. reflection% reflection
Rfree0.265 1239 4.9 %
Rwork0.227 --
obs0.229 25289 100 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 74.27 Å2
Refinement stepCycle: LAST / Resolution: 2.94→39.78 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6025 0 202 0 6227
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0066367
X-RAY DIFFRACTIONf_angle_d1.0318633
X-RAY DIFFRACTIONf_dihedral_angle_d26.395942
X-RAY DIFFRACTIONf_chiral_restr0.0521004
X-RAY DIFFRACTIONf_plane_restr0.0091053
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.94-3.060.33081180.27292628X-RAY DIFFRACTION100
3.06-3.20.33181590.262619X-RAY DIFFRACTION100
3.2-3.370.3061230.24292672X-RAY DIFFRACTION100
3.37-3.580.27071490.23882634X-RAY DIFFRACTION100
3.58-3.850.25031280.2142691X-RAY DIFFRACTION100
3.85-4.240.25411580.20842664X-RAY DIFFRACTION100
4.24-4.850.23891470.21182649X-RAY DIFFRACTION100
4.85-6.110.30431460.24652690X-RAY DIFFRACTION100
6.11-39.780.22241110.21482803X-RAY DIFFRACTION100

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more