Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural snapshots capture nucleotide release at the μ-opioid receptor.
Journal, issue, pages	Nature, Vol. 648, Issue 8094, Page 755-763, Year 2025
Publish date	Nov 5, 2025
Authors	Saif Khan / Aaliyah S Tyson / Mohsen Ranjbar / Zixin Zhang / Jaskaran Singh / Gye Won Han / Cornelius Gati /
PubMed 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.
External links	Nature / PubMed:41193810 / PubMed Central
Methods	EM (single particle)
Resolution	2.73 - 8.78 Å
Structure data	EMDB-71976: Inactive-state naloxone-mu opioid receptor nanobody6 complex - Consensus map Method: EM (single particle) / Resolution: 3.58 Å EMDB-71977: Inactive-state naloxone-mu opioid receptor nanobody6 complex - Locally refined receptor map Method: EM (single particle) / Resolution: 3.4 Å EMDB-71978: Inactive-state naloxone-mu opioid receptor nanobody6 complex - Locally refined fiducal map Method: EM (single particle) / Resolution: 3.12 Å EMDB-71979: Nucleotide-free naloxone-mu opioid receptor Gi1 complex - Consensus map Method: EM (single particle) / Resolution: 3.1 Å EMDB-71980: Nucleotide-free naloxone-mu opioid receptor Gi1 complex - Locally refined receptor map Method: EM (single particle) / Resolution: 3.3 Å EMDB-71981: Nucleotide-free naloxone-mu opioid receptor Gi1 complex - Locally refined Gi map Method: EM (single particle) / Resolution: 3.1 Å EMDB-71982: Latent-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Consensus map Method: EM (single particle) / Resolution: 3.82 Å EMDB-71983: Latent-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined receptor map Method: EM (single particle) / Resolution: 3.97 Å EMDB-71984: Latent-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined Gi map Method: EM (single particle) / Resolution: 3.15 Å EMDB-71985: Unlatched-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Consensus map Method: EM (single particle) / Resolution: 3.2 Å EMDB-71986: Unlatched-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined receptor map Method: EM (single particle) / Resolution: 3.2 Å EMDB-71987: Unlatched-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined Gi map Method: EM (single particle) / Resolution: 3.0 Å EMDB-71988: Primed-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Consensus map Method: EM (single particle) / Resolution: 3.01 Å EMDB-71989: Primed-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined receptor map Method: EM (single particle) / Resolution: 3.05 Å EMDB-71990: Primed-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined Gi map Method: EM (single particle) / Resolution: 2.91 Å EMDB-71991: Engaged-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) - Consensus map Method: EM (single particle) / Resolution: 3.17 Å EMDB-71992: Engaged-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined receptor map Method: EM (single particle) / Resolution: 3.35 Å EMDB-71993: Engaged-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined Gi map Method: EM (single particle) / Resolution: 2.98 Å EMDB-71998: Primed-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) - Consensus map Method: EM (single particle) / Resolution: 2.86 Å EMDB-71999: Primed-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined receptor map Method: EM (single particle) / Resolution: 3.01 Å EMDB-72000: Primed-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) - Locally refined Gi GDP map Method: EM (single particle) / Resolution: 2.73 Å 72001 9pxu EMDB-72001, PDB-9pxu: Inactive-state naloxone-mu opioid receptor nanobody6 complex Method: EM (single particle) / Resolution: 3.4 Å 72002 9pxv EMDB-72002, PDB-9pxv: Nucleotide-free naloxone-mu opioid receptor Gi1 complex Method: EM (single particle) / Resolution: 3.02 Å 72003 9pxw EMDB-72003, PDB-9pxw: Latent-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) Method: EM (single particle) / Resolution: 3.8 Å 72004 9pxx EMDB-72004, PDB-9pxx: Unlatched-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) Method: EM (single particle) / Resolution: 3.1 Å 72005 9pxy EMDB-72005, PDB-9pxy: Primed-state naloxone-mu opioid receptor-Gi GDPbS complex (rebound) Method: EM (single particle) / Resolution: 3.0 Å 72006 9py2 EMDB-72006, PDB-9py2: Engaged-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) Method: EM (single particle) / Resolution: 3.16 Å 72008 9py4 EMDB-72008, PDB-9py4: Primed-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound) Method: EM (single particle) / Resolution: 2.78 Å EMDB-72022: Latent-state loperamide-mu opioid receptor-Gi GDP complex (constant GDP) - Consensus map Method: EM (single particle) / Resolution: 8.78 Å EMDB-72023: Latent-state loperamide-mu opioid receptor-Gi GDP complex (constant GDP) - Locally refined map Method: EM (single particle) / Resolution: 8.27 Å EMDB-72024: Engaged-state loperamide-mu opioid receptor-Gi GDP complex (constant GDP) - Consensus map Method: EM (single particle) / Resolution: 6.4 Å EMDB-72025: Engaged-state loperamide-mu opioid receptor-Gi GDP complex (constant GDP) - Locally refined map Method: EM (single particle) / Resolution: 4.44 Å EMDB-72026: Open-AHD loperamide-mu opioid receptor-Gi GDP complex (constant GDP) - Consensus map Method: EM (single particle) / Resolution: 4.24 Å EMDB-72027: Open-AHD loperamide-mu opioid receptor-Gi GDP complex (constant GDP) - Locally refined receptor map Method: EM (single particle) / Resolution: 4.16 Å
Chemicals	PDB-1apv: CRYSTALLOGRAPHIC ANALYSIS OF TRANSITION STATE MIMICS BOUND TO PENICILLOPEPSIN: DIFLUOROSTATINE-AND DIFLUOROSTATONE-CONTAINING PEPTIDES ChemComp-NA: Unknown entry ChemComp-CLR: CHOLESTEROL ChemComp-VSN: 5'-O-[(R)-hydroxy(thiophosphonooxy)phosphoryl]guanosine PDB-1cmv: HUMAN CYTOMEGALOVIRUS PROTEASE
Source	homo sapiens (human) synthetic construct (others) escherichia coli (E. coli)
Keywords	MEMBRANE PROTEIN / G protein coupled receptor / Mu Opioid receptor / Naloxone / GDP / Loperamide