PDF(Pubmed)
Abstract：
Odorant receptors (ORs) expressed in mammalian olfactory sensory neurons are essential for the sense of smell. However, structure-function studies of many ORs are hampered by unsuccessful heterologous expression. To understand and eventually overcome this bottleneck, we performed heterologous expression and functional assays of over 80 OR variants and chimeras. Combined with literature data and machine learning, we found that the transmembrane domain 4 (TM4) and its interactions with neighbor residues are important for OR functional expression. The data highlight critical roles of T4.62 therein. ORs that fail to reach the cell membrane can be rescued by modifications in TM4. Consequently, such modifications in MOR256-3 (Olfr124) also alter OR responses to odorants. T1614.62 P causes the retention of MOR256-3 in the endoplasmic reticulum (ER), while T1614.62 P/T1484.49 A reverses the retention and makes receptor trafficking to cell membrane. This study offers new clues toward wide-range functional studies of mammalian ORs.
摘要：
在哺乳动物嗅觉感觉神经元中表达的气味受体（ORs）对于嗅觉是必不可少的。然而,许多ORs的结构功能研究受到不成功的异源表达的阻碍。要理解并最终克服这一瓶颈，我们对80多个OR变体和嵌合体进行了异源表达和功能测定.结合文献资料和机器学习，我们发现跨膜结构域4（TM4）及其与相邻残基的相互作用对于OR功能表达很重要。数据突出了其中T4.62的关键作用。无法到达细胞膜的OR可以通过TM4中的修饰来挽救。因此,MOR256-3（Olfr124）中的此类修饰也改变了对气味剂的OR反应。T1614.62P导致MOR256-3在内质网(ER)中滞留,而T1614.62P/T1484.49A逆转了保留，并使受体转运到细胞膜。这项研究为哺乳动物ORs的广泛功能研究提供了新的线索。
