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- EMDB-72952: Cis-azomorphine-3 bound mu opioid receptor Gi complex -

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Basic information

Entry
Database: EMDB / ID: EMD-72952
TitleCis-azomorphine-3 bound mu opioid receptor Gi complex
Map data
Sample
  • Complex: Cis-azomorphine-3 bound Mu opioid receptor in complex with heterotrimeric G protein (Gai/b/g)
    • 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: Mu-type opioid receptor
    • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
  • Ligand: CHOLESTEROL
  • Ligand: N-[17-(cyclopropylmethyl)-3,14-dihydroxy-5alpha-4,5-epoxymorphinan-6beta-yl]-N-methyl-2-{4-[(Z)-phenyldiazenyl]phenyl}acetamide
KeywordsMu Opioid Receptor / G protein coupled receptor / cis-azomorphine-3 / MEMBRANE PROTEIN
Function / homology
Function and homology information


Opioid Signalling / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / G protein-coupled opioid receptor signaling pathway / negative regulation of nitric oxide biosynthetic process / behavioral response to ethanol / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / positive regulation of neurogenesis / regulation of NMDA receptor activity ...Opioid Signalling / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / G protein-coupled opioid receptor signaling pathway / negative regulation of nitric oxide biosynthetic process / behavioral response to ethanol / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / positive regulation of neurogenesis / regulation of NMDA receptor activity / neuropeptide binding / sensory perception / negative regulation of cytosolic calcium ion concentration / regulation of cellular response to stress / transmission of nerve impulse / G-protein alpha-subunit binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / MECP2 regulates neuronal receptors and channels / voltage-gated calcium channel activity / sensory perception of pain / regulation of eating behavior / adenylate cyclase inhibitor activity / 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 / presynaptic modulation of chemical synaptic transmission / adenylate cyclase-inhibiting dopamine receptor signaling pathway / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / regulation of G protein-coupled receptor signaling pathway / cellular response to forskolin / regulation of mitotic spindle organization / Peptide ligand-binding receptors / mast cell degranulation / chemokine-mediated signaling pathway / establishment of mitotic spindle orientation / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / GABA-ergic synapse / G protein-coupled receptor binding / response to peptide hormone / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / cell division / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / GDP binding / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / heterotrimeric G-protein complex / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / presynapse / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / spindle pole / extracellular vesicle / Thrombin signalling through proteinase activated receptors (PARs) / adenylate cyclase-activating G protein-coupled receptor signaling pathway / signaling receptor complex adaptor activity / ciliary basal body / Interleukin-4 and Interleukin-13 signaling / GTPase binding / midbody / G protein activity / cell cortex / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
Similarity search - Function
Mu opioid receptor / Opioid receptor / 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. ...Mu opioid receptor / Opioid receptor / 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 / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Mu-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 / Guanine nucleotide-binding protein G(i) subunit alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.29 Å
AuthorsGati C / Khan S / Han GW
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM144965 United States
National Institutes of Health/National Center for Complementary and Integrative Health (NIH/NCCIH)AT012075 United States
CitationJournal: To Be Published
Title: An opioid efficacy switch for reversible optical control of peripheral analgesia
Authors: Posa L / Romano G / Ji X / Khan S / Paz B / Han GW / Nazarova A / Zaidi S / Pleil K / Katritch V / Gati C / Trauner D / Levitz J
History
DepositionSep 30, 2025-
Header (metadata) releaseOct 14, 2026-
Map releaseOct 14, 2026-
UpdateOct 14, 2026-
Current statusOct 14, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_72952.png

Downloads & links

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Map

FileDownload / File: emd_72952.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.29 Å/pix.
x 256 pix.
= 331.264 Å		1.29 Å/pix.
x 256 pix.
= 331.264 Å		1.29 Å/pix.
x 256 pix.
= 331.264 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.294 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.295
Minimum - Maximum-1.6458817 - 2.791225
Average (Standard dev.)0.008462668 (±0.036877472)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 331.264 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Cis-azomorphine-3 bound Mu opioid receptor in complex with hetero...

EntireName: Cis-azomorphine-3 bound Mu opioid receptor in complex with heterotrimeric G protein (Gai/b/g)
Components
  • Complex: Cis-azomorphine-3 bound Mu opioid receptor in complex with heterotrimeric G protein (Gai/b/g)
    • 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: Mu-type opioid receptor
    • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
  • Ligand: CHOLESTEROL
  • Ligand: N-[17-(cyclopropylmethyl)-3,14-dihydroxy-5alpha-4,5-epoxymorphinan-6beta-yl]-N-methyl-2-{4-[(Z)-phenyldiazenyl]phenyl}acetamide

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Supramolecule #1: Cis-azomorphine-3 bound Mu opioid receptor in complex with hetero...

SupramoleculeName: Cis-azomorphine-3 bound Mu opioid receptor in complex with heterotrimeric G protein (Gai/b/g)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 150 kDa/nm

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Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 39.839469 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: HHHHHHHHHH LEVLFQGPGS SGSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSR LLVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE L AGHTGYLS ...String:
HHHHHHHHHH LEVLFQGPGS SGSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSR LLVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE L AGHTGYLS CCRFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CR QTFTGHE SDINAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDA LKADRA GVLAGHDNRV SCLGVTDDGM AVATGSWDSF LKIWN

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

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Macromolecule #2: 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: 2 / 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

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Macromolecule #3: Mu-type opioid receptor

MacromoleculeName: Mu-type opioid receptor / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 69.540367 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MKTIIALSYI FCLVFADYKD HDGDYKDHDI DYKDDDDKLH HHHHHHHHHL EVLFQGPGSG SADLEDNWET LNDNLKVIEK ADNAAQVKD ALTKMRAAAL DAQKATPPKL EDKSPDSPEM KDFRHGFDIL VGQIDDALKL ANEGKVKEAQ AAAEQLKTTR N AYIQKYLG ...String:
MKTIIALSYI FCLVFADYKD HDGDYKDHDI DYKDDDDKLH HHHHHHHHHL EVLFQGPGSG SADLEDNWET LNDNLKVIEK ADNAAQVKD ALTKMRAAAL DAQKATPPKL EDKSPDSPEM KDFRHGFDIL VGQIDDALKL ANEGKVKEAQ AAAEQLKTTR N AYIQKYLG TGSDSSAAPT NASNCTDALA YSSCSPAPSP GSWVNLSHLD GNLSDPCGPN RTDLGGRDSL CPPTGSPSMI TA ITIMALY SIVCVVGLFG NFLVMYVIVR YTKMKTATNI YIFNLALADA LATSTLPFQS VNYLMGTWPF GTILCKIVIS IDY YNMFTS IFTLCTMSVD RYIAVCHPVK ALDFRTPRNA KIINVCNWIL SSAIGLPVMF MATTKYRQGS IDCTLTFSHP TWYW ENLLK ICVFIFAFIM PVLIITVCYG LMILRLKSVR MLSGSKEKDR NLRRITRMVL VVVAVFIVCW TPIHIYVIIK ALVTI PETT FQTVSWHFCI ALGYTNSCLN PVLYAFLDEN FKRCFREFCI PTSSNIEQQN STRIRQNTRD HPSTANTVDR TNHQLE NLE AETAPLPAAA LEVLFQGPGS WSHPQFEKGG GSGGGSGGSS AWSHPQFEKH HHHHHHHHH

UniProtKB: Mu-type opioid receptor

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Macromolecule #4: Guanine nucleotide-binding protein G(i) subunit alpha-1

MacromoleculeName: Guanine nucleotide-binding protein G(i) subunit alpha-1
type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.415031 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String:
MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF

UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1

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Macromolecule #5: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 5 / Number of copies: 3 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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Macromolecule #6: N-[17-(cyclopropylmethyl)-3,14-dihydroxy-5alpha-4,5-epoxymorphina...

MacromoleculeName: N-[17-(cyclopropylmethyl)-3,14-dihydroxy-5alpha-4,5-epoxymorphinan-6beta-yl]-N-methyl-2-{4-[(Z)-phenyldiazenyl]phenyl}acetamide
type: ligand / ID: 6 / Number of copies: 1 / Formula: A1BK1
Molecular weightTheoretical: 578.701 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1.1 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Number grids imaged: 1 / Average electron dose: 51.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsCalibrated magnification: 130000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: AB INITIO
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.29 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v4.3.1) / Number images used: 191338
Initial angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: cryoSPARC (ver. v4.3.1)
Final angle assignmentType: ANGULAR RECONSTITUTION

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