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- PDB-10tl: Cryo-EM structure of human MOR bound with DAMGO and BMS986187 -

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Basic information

Entry
Database: PDB / ID: 10tl
TitleCryo-EM structure of human MOR bound with DAMGO and BMS986187
Components
  • Mu-type opioid receptor
  • TYR-DAL-GLY-MEA-ETA
KeywordsMEMBRANE PROTEIN / analgesics / GPCR / allosteric modulation
Function / homology
Function and homology information


Opioid Signalling / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / regulation of cellular response to stress / G protein-coupled opioid receptor signaling pathway / negative regulation of nitric oxide biosynthetic process / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / behavioral response to ethanol / regulation of NMDA receptor activity ...Opioid Signalling / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / regulation of cellular response to stress / G protein-coupled opioid receptor signaling pathway / negative regulation of nitric oxide biosynthetic process / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / behavioral response to ethanol / regulation of NMDA receptor activity / neuropeptide binding / positive regulation of neurogenesis / sensory perception / negative regulation of cytosolic calcium ion concentration / G-protein alpha-subunit binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / voltage-gated calcium channel activity / MECP2 regulates neuronal receptors and channels / sensory perception of pain / Peptide ligand-binding receptors / neuropeptide signaling pathway / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein activation / G-protein beta-subunit binding / Interleukin-4 and Interleukin-13 signaling / G alpha (i) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / perikaryon / positive regulation of ERK1 and ERK2 cascade / endosome / neuron projection / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / axon / synapse / dendrite / endoplasmic reticulum / Golgi apparatus / plasma membrane
Similarity search - Function
Mu opioid receptor / Opioid receptor / 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.
Similarity search - Domain/homology
DAMGO / : / CHOLESTEROL / Mu-type opioid receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsZhang, H. / Zilberg, G. / Parpounas, A. / Warren, A.L. / Wacker, D. / Abraham, A.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA) United States
CitationJournal: To Be Published
Title: cryo-EM structure of human MOR-Gi1 complex protein bound with DAMGO and BMS986187
Authors: Zhang, H. / Zilberg, G. / Parpounas, A. / Warren, A.L. / Wacker, D. / Abraham, A.
History
DepositionFeb 8, 2026Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 27, 2026Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
R: Mu-type opioid receptor
S: TYR-DAL-GLY-MEA-ETA
F: Mu-type opioid receptor
H: TYR-DAL-GLY-MEA-ETA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,21714
Polymers88,1834
Non-polymers4,03410
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Mu-type opioid receptor / M-OR-1 / MOR-1 / Mu opiate receptor / Mu opioid receptor / MOP / hMOP


Mass: 43577.840 Da / Num. of mol.: 2 / Mutation: F158W
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: OPRM1, MOR1 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P35372
#2: Protein/peptide TYR-DAL-GLY-MEA-ETA


Type: Peptide-like / Class: Synthetic opioid / Mass: 513.587 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: DAMGO
#3: Chemical
ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C27H46O
#4: Chemical ChemComp-A1D6B / 3,3,6,6-tetramethyl-9-[4-[(2-methylphenyl)methoxy]phenyl]-4,5,7,9-tetrahydro-2~{H}-xanthene-1,8-dione / BMS986187


Mass: 470.599 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C31H34O4 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: mu-opioid receptor complexed with DAMGO / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 4110 nm / Nominal defocus min: 470 nm / Cs: 2.7 mm
Image recordingAverage exposure time: 1.5 sec. / Electron dose: 33.82 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 9298

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2PHENIX(1.19.2_4158: ???)model refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 101558 / Symmetry type: POINT
RefinementResolution: 3.5→253.2 Å / SU ML: 0.6 / σ(F): 1.03 / Phase error: 47.08 / Stereochemistry target values: MLHL
RfactorNum. reflection% reflection
Rfree0.4016 1969 0.25 %
Rwork0.4083 --
obs0.4083 792182 99.93 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00314786
ELECTRON MICROSCOPYf_angle_d0.53120130
ELECTRON MICROSCOPYf_dihedral_angle_d13.1765404
ELECTRON MICROSCOPYf_chiral_restr0.0422352
ELECTRON MICROSCOPYf_plane_restr0.0032496
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.5-3.590.45011320.522456529ELECTRON MICROSCOPY100
3.59-3.680.46751440.479956440ELECTRON MICROSCOPY100
3.69-3.790.47111440.470656332ELECTRON MICROSCOPY100
3.79-3.920.50021440.470756410ELECTRON MICROSCOPY100
3.92-4.060.49881240.506256544ELECTRON MICROSCOPY100
4.06-4.220.39191560.448156834ELECTRON MICROSCOPY100
4.22-4.410.37291320.387856243ELECTRON MICROSCOPY100
4.41-4.640.42411320.366756417ELECTRON MICROSCOPY100
4.64-4.930.36051320.366856443ELECTRON MICROSCOPY100
4.93-5.310.35791320.361956414ELECTRON MICROSCOPY100
5.31-5.850.38621560.399856946ELECTRON MICROSCOPY100
5.85-6.690.36631440.428855950ELECTRON MICROSCOPY100
6.7-8.440.42961440.42356823ELECTRON MICROSCOPY100
8.44-253.20.35221530.341255888ELECTRON MICROSCOPY99

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