通过II类嗅觉受体介导的脂肪酸气味检测的机制见解
Xiang Han1, Ming-Hui Zhang2, Nai-Kang Rong1
1Shandong Provincial Third Hospital, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; NHC Key Laboratory of Otorhinolaryngology, Qilu hospital and New Cornerstone Science Laboratory, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Cell
|January 22, 2026
概括
研究人员发现了II类气味受体 (ORs) 识别气味分子的结构基础. 这项研究揭示了关键的相互作用和激活机制,为潜在的针对嗅觉受体的药物开发铺平了道路.
科学领域:
- 嗅觉受体研究
- 结构生物学
- 嗅觉的分子机制
背景情况:
- 嗅觉是一种由成千上万的嗅觉受体 (ORs) 介导的基本感官.
- 对于II类OR的疏水性气味剂的识别机制尚不清楚.
- 第二类手术室在检测各种气味分子方面发挥着至关重要的作用.
研究的目的:
- 在II类OR中阐明连体识别和激活机制的结构基础.
- 呈现II类或Olfr110类的冷电子显微镜 (cryo-EM) 结构.
- 描述OR5亚家族中参与联体结合的保存基因.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定高分辨率结构.
- 用体 (PL45, 12(S) -HEPE) 和G蛋白 (Gs) 对Olfr110的复杂形成分析.
- 对连接体结合口袋,极性网络和 π-π 相互作用的结构分析.
主要成果:
- 在Olfr110中发现异常大的疏水口袋,容纳不和脂肪酸代谢物 (UFAM),如PL45和12S-HEPE.
- 确定了对连接体结合至关重要的极性网络和π-π相互作用.
- 在类型IIOR5亚家族中进行了鉴定,以识别连接物.
- 观察到细胞外循环3 (ECL3) 的向内移动以及Olfr110的非传统激活机制.
- 在G蛋白界面上的详细常见和独特的相互作用.
结论:
- 这项研究为了解II类OR的气味识别提供了结构基础.
- 发现了一种涉及ECL3运动的非传统激活机制.
- 这些发现为G蛋白相互作用提供了洞察力,有可能指导嗅觉相关疗法的药物开发.
相关概念视频
Receptor-mediated Endocytosis
110.7K
Overview
110.7K
Receptor-mediated Endocytosis
7.6K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
7.6K
Overview of Fatty Acid Metabolism
36.7K
Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
36.7K
Olfactory Receptors: Location and Structure
11.3K
The process of olfaction, also known as the sense of smell, is a sophisticated chemical response system. The specialized sensory neurons that facilitate this process, known as olfactory receptor neurons, are situated in an upper segment of the nasal cavity, known as the olfactory epithelium. Olfactory sensory neurons are bipolar, with their dendrites extending from the epithelium's apex into the mucus that lines the nasal cavity. Airborne molecules, when inhaled, traverse the olfactory...
11.3K
Internal Receptors
74.3K
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.3K
Drug Classes and Categories
3.1K
Drugs can be classified according to their chemical composition or their intended therapeutic application. For instance, anti-infective agents that possess the ability to eliminate pathogens or suppress their growth and reproduction can be grouped based on the organisms they target or their chemical structure. Furthermore, drugs can be divided into prescription, nonprescription, or controlled substances. Prescription medications, such as antibiotics, require oversight from a licensed healthcare...
3.1K


