[English] 日本語
Yorodumi
- EMDB-71987: Unlatched-state naloxone-mu opioid receptor-Gi GDPbS complex (reb... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-71987
TitleUnlatched-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined Gi map
Map dataUnlatched-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined Gi map
Sample
  • Complex: Naloxone-mu opioid receptor in complex with Gai-GDPbS, Gb1 and Gg2
KeywordsG protein coupled receptor / Mu Opioid receptor / Naloxone / MEMBRANE PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 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: Nature / Year: 2025
Title: Structural snapshots capture nucleotide release at the μ-opioid receptor.
Authors: Saif Khan / Aaliyah S Tyson / Mohsen Ranjbar / Zixin Zhang / Jaskaran Singh / Gye Won Han / Cornelius Gati /
Abstract: As a member of the G protein-coupled receptor superfamily, the μ-opioid receptor (MOR) activates heterotrimeric G proteins by opening the Gα α-helical domain (AHD) to enable GDP-GTP exchange, ...As a member of the G protein-coupled receptor superfamily, the μ-opioid receptor (MOR) activates heterotrimeric G proteins by opening the Gα α-helical domain (AHD) to enable GDP-GTP exchange, with GDP release representing the rate-limiting step. Here, using pharmacological assays, we show that agonist efficacy correlates with decreased GDP affinity, promoting GTP exchange, whereas antagonists increase GDP affinity, dampening activation. Further investigating this phenomenon, we provide 8 unique structural models and 16 cryogenic electron microscopy maps of MOR with naloxone or loperamide, capturing several intermediate conformations along the activation pathway. These include four GDP-bound states with previously undescribed receptor-G protein interfaces, AHD arrangements and transitions in the nucleotide-binding pocket required for GDP release. Naloxone stalls MOR in a 'latent' state, whereas loperamide promotes an 'engaged' state, which is structurally poised for opening of the AHD domain and subsequent GDP release. These findings, supported by molecular dynamics simulations, identify GDP-bound intermediates and AHD conformations as key determinants of nucleotide exchange rates, providing structural and mechanistic insights into G protein activation and ligand efficacy with broad implications for G protein-coupled receptor pharmacology.
History
DepositionAug 6, 2025-
Header (metadata) releaseNov 12, 2025-
Map releaseNov 12, 2025-
UpdateNov 19, 2025-
Current statusNov 19, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_71987.png

Downloads & links

-
Map

FileDownload / File: emd_71987.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationUnlatched-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined Gi map
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: 0.183
Minimum - Maximum-1.3598833 - 2.3042154
Average (Standard dev.)-0.00031831718 (±0.029097356)
SymmetrySpace group: 1
Details

EMDB XML:

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

-
Supplemental data

-
Additional map: Additional Map

Fileemd_71987_additional_1.map
AnnotationAdditional Map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half Map A

Fileemd_71987_half_map_1.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half Map B

Fileemd_71987_half_map_2.map
AnnotationHalf Map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Naloxone-mu opioid receptor in complex with Gai-GDPbS, Gb1 and Gg2

EntireName: Naloxone-mu opioid receptor in complex with Gai-GDPbS, Gb1 and Gg2
Components
  • Complex: Naloxone-mu opioid receptor in complex with Gai-GDPbS, Gb1 and Gg2

-
Supramolecule #1: Naloxone-mu opioid receptor in complex with Gai-GDPbS, Gb1 and Gg2

SupramoleculeName: Naloxone-mu opioid receptor in complex with Gai-GDPbS, Gb1 and Gg2
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 130 kDa/nm

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
Component:
ConcentrationFormulaName
40.0 mMHEPESHEPES
100.0 mMNaClsodium chloride
0.00075 %LMNGdetergent
0.00025 %GDNdetergent
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Support film - Material: GOLD / Support film - topology: HOLEY ARRAY
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (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 opticsIllumination 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 / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionSoftware - Name: cryoSPARC (ver. v4.3.1) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: Ab initio
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v4.3.1) / Number images used: 146381
Initial angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: cryoSPARC (ver. v4.3.1)
Final angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: cryoSPARC (ver. v4.3.1)
Final 3D classificationNumber classes: 2 / Software - Name: cryoSPARC (ver. v4.3.1)
FSC plot (resolution estimation)

+
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