[English] 日本語
Yorodumi
- EMDB-27806: GR89,696 bound Kappa Opioid Receptor in complex with gustducin -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-27806
TitleGR89,696 bound Kappa Opioid Receptor in complex with gustducin
Map datadeep sharp
Sample
  • Complex: GR89,696 bound Kappa Opioid Receptor in complex with gustducin
    • Protein or peptide: Kappa-type opioid receptor
    • Protein or peptide: G alpha gustducin protein
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Protein or peptide: ScFv16 protein
  • Ligand: methyl (3R)-4-[(3,4-dichlorophenyl)acetyl]-3-[(pyrrolidin-1-yl)methyl]piperazine-1-carboxylate
KeywordsGPCR / Kappa opioid receptor / G protein / MEMBRANE PROTEIN
Function / homology
Function and homology information


response to acrylamide / regulation of saliva secretion / dynorphin receptor activity / sensory perception of temperature stimulus / positive regulation of eating behavior / adenylate cyclase-inhibiting opioid receptor signaling pathway / G protein-coupled opioid receptor activity / negative regulation of luteinizing hormone secretion / G protein-coupled opioid receptor signaling pathway / positive regulation of dopamine secretion ...response to acrylamide / regulation of saliva secretion / dynorphin receptor activity / sensory perception of temperature stimulus / positive regulation of eating behavior / adenylate cyclase-inhibiting opioid receptor signaling pathway / G protein-coupled opioid receptor activity / negative regulation of luteinizing hormone secretion / G protein-coupled opioid receptor signaling pathway / positive regulation of dopamine secretion / sensory perception / positive regulation of potassium ion transmembrane transport / maternal behavior / conditioned place preference / receptor serine/threonine kinase binding / neuropeptide binding / positive regulation of p38MAPK cascade / eating behavior / behavioral response to cocaine / neuropeptide signaling pathway / estrous cycle / MECP2 regulates neuronal receptors and channels / axon terminus / sensory perception of pain / T-tubule / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / sarcoplasmic reticulum / locomotory behavior / cellular response to glucose stimulus / response to nicotine / response to insulin / 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 / G-protein activation / 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 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / synaptic vesicle membrane / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / response to estrogen / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / 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 / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / 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 / presynaptic membrane / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / fibroblast proliferation / G alpha (i) signalling events / G alpha (s) signalling events / cellular response to lipopolysaccharide / chemical synaptic transmission / G alpha (q) signalling events / perikaryon / defense response to virus / postsynaptic membrane / response to ethanol / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / neuron projection / immune response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / dendrite / synapse / protein-containing complex binding / signal transduction / mitochondrion
Similarity search - Function
Kappa opioid receptor / Opioid receptor / Serpentine type 7TM GPCR chemoreceptor Srsx / 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 ...Kappa opioid receptor / Opioid receptor / Serpentine type 7TM GPCR chemoreceptor Srsx / 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 subunit / 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) / 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. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
Kappa-type opioid receptor / 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
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.61 Å
AuthorsFay JF / Che T
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM143061 United States
CitationJournal: Nature / Year: 2023
Title: Ligand and G-protein selectivity in the κ-opioid receptor.
Authors: Jianming Han / Jingying Zhang / Antonina L Nazarova / Sarah M Bernhard / Brian E Krumm / Lei Zhao / Jordy Homing Lam / Vipin A Rangari / Susruta Majumdar / David E Nichols / Vsevolod ...Authors: Jianming Han / Jingying Zhang / Antonina L Nazarova / Sarah M Bernhard / Brian E Krumm / Lei Zhao / Jordy Homing Lam / Vipin A Rangari / Susruta Majumdar / David E Nichols / Vsevolod Katritch / Peng Yuan / Jonathan F Fay / Tao Che /
Abstract: The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders. However, the development of KOR analgesics has ...The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders. However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects. The initiation of KOR signalling requires the G-family proteins including the conventional (G, G, G, G and G) and nonconventional (G and G) subtypes. How hallucinogens exert their actions through KOR and how KOR determines G-protein subtype selectivity are not well understood. Here we determined the active-state structures of KOR in a complex with multiple G-protein heterotrimers-G, G, G and G-using cryo-electron microscopy. The KOR-G-protein complexes are bound to hallucinogenic salvinorins or highly selective KOR agonists. Comparisons of these structures reveal molecular determinants critical for KOR-G-protein interactions as well as key elements governing G-family subtype selectivity and KOR ligand selectivity. Furthermore, the four G-protein subtypes display an intrinsically different binding affinity and allosteric activity on agonist binding at KOR. These results provide insights into the actions of opioids and G-protein-coupling specificity at KOR and establish a foundation to examine the therapeutic potential of pathway-selective agonists of KOR.
History
DepositionAug 8, 2022-
Header (metadata) releaseMay 3, 2023-
Map releaseMay 3, 2023-
UpdateOct 30, 2024-
Current statusOct 30, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_27806.png

Downloads & links

-
Map

FileDownload / File: emd_27806.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationdeep sharp
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.88 Å/pix.
x 288 pix.
= 253.44 Å		0.88 Å/pix.
x 288 pix.
= 253.44 Å		0.88 Å/pix.
x 288 pix.
= 253.44 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.88 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0695
Minimum - Maximum-0.0206857 - 1.8582568
Average (Standard dev.)0.0009897104 (±0.020072076)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 253.44 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: bfact sharp

Fileemd_27806_additional_1.map
Annotationbfact sharp
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half B

Fileemd_27806_half_map_1.map
Annotationhalf B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half A

Fileemd_27806_half_map_2.map
Annotationhalf A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : GR89,696 bound Kappa Opioid Receptor in complex with gustducin

EntireName: GR89,696 bound Kappa Opioid Receptor in complex with gustducin
Components
  • Complex: GR89,696 bound Kappa Opioid Receptor in complex with gustducin
    • Protein or peptide: Kappa-type opioid receptor
    • Protein or peptide: G alpha gustducin protein
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Protein or peptide: ScFv16 protein
  • Ligand: methyl (3R)-4-[(3,4-dichlorophenyl)acetyl]-3-[(pyrrolidin-1-yl)methyl]piperazine-1-carboxylate

-
Supramolecule #1: GR89,696 bound Kappa Opioid Receptor in complex with gustducin

SupramoleculeName: GR89,696 bound Kappa Opioid Receptor in complex with gustducin
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Kappa-type opioid receptor

MacromoleculeName: Kappa-type opioid receptor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 32.289387 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GSISPAIPVI ITAVYSVVFV VGLVGNSLVM FVIIRYTKMK TATNIYIFNL ALADALVTTT MPFQSTVYLM NSWPFGDVLC KIVLSIDYY NMFTSIFTLT MMSVDRYIAV CHPVKALDFR TPLKAKIINI CIWLLSSSVG ISAIVLGGTK VREDVDVIEC S LQFPDDDY ...String:
GSISPAIPVI ITAVYSVVFV VGLVGNSLVM FVIIRYTKMK TATNIYIFNL ALADALVTTT MPFQSTVYLM NSWPFGDVLC KIVLSIDYY NMFTSIFTLT MMSVDRYIAV CHPVKALDFR TPLKAKIINI CIWLLSSSVG ISAIVLGGTK VREDVDVIEC S LQFPDDDY SWWDLFMKIC VFIFAFVIPV LIIIVCYTLM ILRLKSVRLL SGSREKDRNL RRITRLVLVV VAVFVVCWTP IH IFILVEA LGSTSHSTAA LSSYYFCIAL GYTNSSLNPI LYAFLDENFK

UniProtKB: Kappa-type opioid receptor

-
Macromolecule #2: G alpha gustducin protein

MacromoleculeName: G alpha gustducin protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.340898 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGSTVSAEDK AAAERSKMID KNLREDAERD ARTVKLLLLG AGESGKATIV KQMKIIHKNG YSEQECMEFK AVIYSNTLQS ILAIVKAMT TLGIDYVNPR SAEDQRQLYA MANTLEDGGM TPQLAEVIKR LWRDPGIQAC FERASEYQLN DSAAYYLNDL D RITASGYV ...String:
MGSTVSAEDK AAAERSKMID KNLREDAERD ARTVKLLLLG AGESGKATIV KQMKIIHKNG YSEQECMEFK AVIYSNTLQS ILAIVKAMT TLGIDYVNPR SAEDQRQLYA MANTLEDGGM TPQLAEVIKR LWRDPGIQAC FERASEYQLN DSAAYYLNDL D RITASGYV PNEQDVLHSR VKTTGIIETQ FSFKDLHFRM FDVGAQRSER KKWIHCFEGV TCIIFCAALS AYDMVLVEDE EV NRMHASL KLFDSICNHK YFSDTSIVLF LNKKDIFQEK VTKVHLSICF PEYTGPNTFE DAGNYIKNQF LDLNLKKEDK EIY SHMTCS TDTQNVKFVF DAVTDIIIKE NLKDCGLF

-
Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.285734 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW ...String:
SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NAICFFPNGN AF ATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGHDNRVSCL GVT DDGMAV ATGSWDSFLK IWN

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

-
Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.861143 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

-
Macromolecule #5: ScFv16 protein

MacromoleculeName: ScFv16 protein / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 26.679721 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String:
DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAA

-
Macromolecule #6: methyl (3R)-4-[(3,4-dichlorophenyl)acetyl]-3-[(pyrrolidin-1-yl)me...

MacromoleculeName: methyl (3R)-4-[(3,4-dichlorophenyl)acetyl]-3-[(pyrrolidin-1-yl)methyl]piperazine-1-carboxylate
type: ligand / ID: 6 / Number of copies: 1 / Formula: U9I
Molecular weightTheoretical: 414.326 Da
Chemical component information

ChemComp-U9I:
methyl (3R)-4-[(3,4-dichlorophenyl)acetyl]-3-[(pyrrolidin-1-yl)methyl]piperazine-1-carboxylate

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE-PROPANE

-
Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number real images: 5752 / Average electron dose: 29.07 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.4 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.61 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 725271
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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