9LDZ

Consensus olfactory receptor consOR6 in complex with Gs trimeric protein

This is a non-PDB format compatible entry.

Summary for 9LDZ

• Entry DOI: 10.2210/pdb9ldz/pdb
• EMDB information: 63010
• Descriptor: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• Functional Keywords: complex, membrane protein, gpcr
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 122841.52

Authors

Wang, T.,Wu, L.J.,Hua, T.,Liu, Z.J. (deposition date: 2025-01-06, release date: 2026-01-28, Last modification date: 2026-02-04)

Primary citation

Wang, T.,Wu, Y.,Wang, L.,Li, S.,Zhao, F.,Wu, L.,Liu, Y.,Qin, J.,Tan, Q.,Liu, J.,Zeng, L.,Chen, Y.,Gao, S.,Shui, W.,Zhao, S.,Hua, T.,Liu, Z.J.
Structural decoding of reversible covalent linkage of odorants in human olfactory receptor OR6A2.
Cell, 2026

PubMed Abstract: Olfactory receptors (ORs) are a diverse superfamily of G protein-coupled receptors responsible for odor detection that are also implicated in non-olfactory physiological functions. OR6A2, a class II OR, selectively senses medium-chain aldehydes and belongs to a cluster of ORs genetically associated with the "soapy" perception of cilantro. It also modulates macrophage-mediated inflammatory responses. Structural studies of ORs have long been challenging. Using a back-mutation strategy, we engineered a functional OR6A2 variant (bmOR6A2) from a consensus OR6 (consOR6). Structures of bmOR6A2 in complex with aldehydes reveal a novel ligand-recognition mechanism involving a reversible Schiff base linkage with residue K, validated by mass spectrometry. By integrating structures of consOR6, molecular dynamics simulations, and functional assays, we identified a conserved DYY triad critical for activation in class II ORs. These findings establish a practical strategy for decoding odorant recognition, offering new insights into olfaction signaling and applications in fragrance and therapeutic development.

PubMed: 41570822
DOI: 10.1016/j.cell.2025.12.017

Experimental method

ELECTRON MICROSCOPY (3.17 Å)