[English] 日本語
Yorodumi
- PDB-7na7: Structures of human ghrelin receptor-Gi complexes with ghrelin an... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7na7
TitleStructures of human ghrelin receptor-Gi complexes with ghrelin and a synthetic agonist
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Antibody fragment
  • Ghrelin-27
  • Growth hormone secretagogue receptor type 1
KeywordsMEMBRANE PROTEIN / GPCR / appetite / energy homeostasis / reward signaling
Function / homology
Function and homology information


ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / cortisol secretion / growth hormone secretagogue receptor activity / regulation of response to food / regulation of hindgut contraction / growth hormone-releasing hormone activity / negative regulation of locomotion involved in locomotory behavior / negative regulation of circadian sleep/wake cycle, REM sleep ...ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / cortisol secretion / growth hormone secretagogue receptor activity / regulation of response to food / regulation of hindgut contraction / growth hormone-releasing hormone activity / negative regulation of locomotion involved in locomotory behavior / negative regulation of circadian sleep/wake cycle, REM sleep / regulation of growth hormone secretion / positive regulation of small intestinal transit / regulation of gastric motility / growth hormone-releasing hormone receptor activity / response to follicle-stimulating hormone / positive regulation of circadian sleep/wake cycle, non-REM sleep / regulation of transmission of nerve impulse / positive regulation of corticotropin secretion / positive regulation of cortisol secretion / gastric acid secretion / positive regulation of growth rate / ghrelin secretion / growth hormone secretion / negative regulation of norepinephrine secretion / negative regulation of macrophage apoptotic process / neuronal dense core vesicle lumen / positive regulation of small intestine smooth muscle contraction / positive regulation of appetite / adult feeding behavior / positive regulation of eating behavior / positive regulation of multicellular organism growth / positive regulation of growth hormone secretion / positive regulation of growth hormone receptor signaling pathway / negative regulation of appetite / actin polymerization or depolymerization / positive regulation of synapse assembly / cartilage development / cellular response to thyroid hormone stimulus / response to growth hormone / positive regulation of vascular endothelial cell proliferation / response to L-glutamate / regulation of postsynapse organization / negative regulation of interleukin-1 beta production / cellular response to insulin-like growth factor stimulus / positive regulation of fatty acid metabolic process / response to dexamethasone / negative regulation of endothelial cell proliferation / negative regulation of interleukin-6 production / positive regulation of sprouting angiogenesis / decidualization / dendrite development / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / peptide hormone binding / response to electrical stimulus / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of tumor necrosis factor production / protein tyrosine kinase activator activity / postsynaptic modulation of chemical synaptic transmission / hormone-mediated signaling pathway / positive regulation of adipose tissue development / regulation of eating behavior / negative regulation of angiogenesis / adenylate cyclase inhibitor activity / response to hormone / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / positive regulation of insulin secretion involved in cellular response to glucose stimulus / regulation of mitotic spindle organization / Peptide ligand-binding receptors / chemokine-mediated signaling pathway / mast cell degranulation / synaptic membrane / positive regulation of insulin secretion / glucose metabolic process / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / negative regulation of inflammatory response / positive regulation of cholesterol biosynthetic process / response to estrogen / G protein-coupled receptor binding / response to peptide hormone / Schaffer collateral - CA1 synapse / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels
Similarity search - Function
Preproghrelin peptide / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Growth hormone secretagogue receptor/motilin receptor / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-protein alpha subunit, group I ...Preproghrelin peptide / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Growth hormone secretagogue receptor/motilin receptor / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-protein alpha subunit, group I / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / Guanine nucleotide-binding protein, beta subunit / G protein beta WD-40 repeat protein / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Immunoglobulins / Immunoglobulin-like / Sandwich / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta
Similarity search - Domain/homology
CHOLESTEROL / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 / Growth hormone secretagogue receptor type 1 / Appetite-regulating hormone
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å
AuthorsLiu, H. / Sun, D. / Sun, J. / Zhang, C.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM128641 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R03TR003306 United States
CitationJournal: Nat Commun / Year: 2021
Title: Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren.
Authors: Heng Liu / Dapeng Sun / Alexander Myasnikov / Marjorie Damian / Jean-Louis Baneres / Ji Sun / Cheng Zhang /
Abstract: The hunger hormone ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its ...The hunger hormone ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its agonistic action on GHSR. Synthetic agonists of GHSR are under clinical evaluation for disorders related to appetite and growth hormone dysregulation. Here, we report high-resolution cryo-EM structures of the GHSR-G signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug. Our structures together with mutagenesis data reveal the molecular basis for the binding of ghrelin and ibutamoren. Structural comparison suggests a salt bridge and an aromatic cluster near the agonist-binding pocket as important structural motifs in receptor activation. Notable structural variations of the G and GHSR coupling are observed in our cryo-EM analysis. Our results provide a framework for understanding GHSR signaling and developing new GHSR agonist drugs.
History
DepositionJun 20, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 15, 2021Provider: repository / Type: Initial release

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-24267
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(i) subunit alpha-1
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
N: Antibody fragment
R: Growth hormone secretagogue receptor type 1
L: Ghrelin-27
hetero molecules


Theoretical massNumber of molelcules
Total (without water)155,5948
Polymers154,8206
Non-polymers7732
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area14120 Å2
ΔGint-68 kcal/mol
Surface area47760 Å2

-
Components

-
Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG

#1: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1 / Adenylate cyclase-inhibiting G alpha protein


Mass: 40429.059 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1
Production host: Insect expression vector pBlueBacmsGCA1His (others)
References: UniProt: P63096
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37417.918 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1
Production host: Insect expression vector pBlueBacmsGCA1His (others)
References: UniProt: P62873
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7859.173 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2
Production host: Insect expression vector pBlueBacmsGCA1His (others)
References: UniProt: P59768

-
Antibody / Protein / Protein/peptide / Non-polymers , 4 types, 5 molecules NRL

#4: Antibody Antibody fragment


Mass: 26236.244 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse)
Production host: Insect expression vector pBlueBacmsGCA1His (others)
#5: Protein Growth hormone secretagogue receptor type 1 / GHS-R / GH-releasing peptide receptor / GHRP / Ghrelin receptor


Mass: 41406.410 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GHSR
Production host: Insect expression vector pBlueBacmsGCA1His (others)
References: UniProt: Q92847
#6: Protein/peptide Ghrelin-27


Mass: 1471.657 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q9UBU3
#7: Chemical ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H46O / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Complex of GHSR-Gi-ghrelin / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Insect expression vector pBlueBacmsGCA1His (others)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 82 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 280046 / Symmetry type: POINT

+
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://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