山东大学Jin-Peng Sun小组的研究开发出了II类嗅觉受体介导的脂肪酸气味检测机制。该项研究成果发表在2026年1月21日出版的《细胞》上。
该课题组展示了II类OR Olfr110与不饱和脂肪酸代谢物（UFAM） PL45， Gs和cons-OR5络合的冷冻电镜（cryo-EM）结构。结构研究揭示了一个异常大的疏水口袋，可容纳PL45和内源性受体激动剂12(S)-羟基二碳五烯酸（12(S)-HEPE）。该口袋由极性残基和芳香残基阵列装饰，分别构成极性网络和与天然激动剂PL45的π-π相互作用。II型OR5亚家族中负责配体识别的保守基序被表征。细胞外环3 （ECL3）的向内运动和一种非常规的激活机制是Olfr110激活的基础。在G蛋白界面上，Olfr110表现出共同和独特的相互作用。总的来说，该团队揭示了气味识别的结构基础和II类ORs的激活机制，这可能有助于针对这些受体的药物开发。
据介绍，嗅觉是由气味受体（ORs）的指令介导的基本感觉之一。疏水和挥发性气味分子如何被II类ORs识别仍然是未知的。
附：英文原文
Title: Mechanistic insights into fatty acid odor detection mediated by class II olfactory receptors
Author: Xiang Han, Ming-Hui Zhang, Nai-Kang Rong, Kong-Kai Zhu, Yuan Pei, Xiao-Yan Ge, Qi Liu, Huan Lu, Jing Liu, Li-Jun Zhang, Hong-Qiang Bao, Jia-Hao Pi, Lei Fan, Yu Fu, Xu-Hang Shao, Wen-Qi Yan, Xi-He Gao, Ming-Yue Zhang, Lu-Lu Guo, Yan Lu, Shang-Lei Ning, Hua Zhang, Yun-Fei Xu, Xiao-Ya Feng, Jie Cheng, Ming Xia, Qian Li, Xiao Yu, Fan Yang, Jin-Peng Sun
Issue&Volume: 2026-01-21
Abstract: Smell is one of the fundamental senses mediated by thousands of odorant receptors (ORs). How hydrophobic and volatile odor molecules are recognized by class II ORs remains elusive. Here, we present cryo-electron microscopy (cryo-EM) structures of class II OR Olfr110 complexed with the unsaturated fatty acid metabolite (UFAM) PL45, Gs, and cons-OR5. The structural study revealed an unusually large hydrophobic pocket accommodating PL45 and the endogenous agonist 12(S)-hydroxyeicosapentaenoic acid (12(S)-HEPE). This pocket is decorated with polar residues and aromatic residue arrays, constituting polar networks and π-π interactions with the natural agonist PL45, respectively. Conserved motifs in the type II OR5 subfamily responsible for ligand recognition are characterized. The inward movement of extracellular loop 3 (ECL3) and an unconventional activation mechanism underlie Olfr110 activation. At the G protein interface, Olfr110 displays common and unique interactions. Overall, we revealed the structural basis of odor recognition and the activation mechanism of class II ORs, which may facilitate drug development targeting these receptors.
DOI: 10.1016/j.cell.2025.12.018
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01431-X