Mammalian odorant receptor tuning breadth persists across distinct odorant panels.
Mammalian odorant receptor tuning breadth persists across distinct odorant panels.
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DOI：
10.1371/journal.pone.0185329
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Luetje CW
中科院分区：
文献类型：
--
作者：
Kepchia D;Sherman B;Haddad R;Luetje CW
哺乳动物气味受体的分子接受范围(MRR)是激活气味受体的气味结构集合，而这些气味结构在气味空间中的分布是气味受体的调谐宽度。调谐宽度的变化被认为是ORS的一个重要特性，这些受体的MRR从狭义到宽调不等。然而，定义OR的调谐宽度是一项技术挑战。出于实际原因，广泛覆盖气味空间的筛选板必须仅限于对该空间中许多潜在结构的稀疏覆盖。当用这样的面板筛选时，气味特性不同但调谐宽度相同的OR可能会因为偶然而出现不同的调谐宽度。我们假设ORs会在不同的气味面板上保持它们的调谐宽度。我们构建了一个新的筛选板，它广泛分布在估计的气味空间，包含与以前的板不同的化合物。我们使用这个新的筛选小组测试了几个以前被描述为具有不同调谐宽度的小鼠OR。在非洲爪哇卵母细胞中表达ORs，并用双电极电压钳电生理学方法进行检测。MOR256-17，一种以前被描述为宽调的OR，对我们新筛选小组中的九种新化合物做出了反应，这些化合物结构多样化，广泛分布在估计的气味空间中。MOR256-22是一种先前被描述为窄调的OR，它对一个结构上类似于该受体的已知配体的单一新化合物起反应。MOR174-9是一种具有良好特性的受体，具有狭窄的MRR，在我们的新小组中对任何新化合物都没有反应。这些结果支持这样一种观点，即这三个OR之间的调谐宽度的变化不是筛选方案的产物，而是受体的内在属性。
The molecular receptive range (MRR) of a mammalian odorant receptor (OR) is the set of odorant structures that activate the OR, while the distribution of these odorant structures across odor space is the tuning breadth of the OR. Variation in tuning breadth is thought to be an important property of ORs, with the MRRs of these receptors varying from narrowly to broadly tuned. However, defining the tuning breadth of an OR is a technical challenge. For practical reasons, a screening panel that broadly covers odor space must be limited to sparse coverage of the many potential structures in that space. When screened with such a panel, ORs with different odorant specificities, but equal tuning breadths, might appear to have different tuning breadths due to chance. We hypothesized that ORs would maintain their tuning breadths across distinct odorant panels. We constructed a new screening panel that was broadly distributed across an estimated odor space and contained compounds distinct from previous panels. We used this new screening panel to test several murine ORs that were previously characterized as having different tuning breadths. ORs were expressed in Xenopus laevis oocytes and assayed by two-electrode voltage clamp electrophysiology. MOR256-17, an OR previously characterized as broadly tuned, responded to nine novel compounds from our new screening panel that were structurally diverse and broadly dispersed across an estimated odor space. MOR256-22, an OR previously characterized as narrowly tuned, responded to a single novel compound that was structurally similar to a previously known ligand for this receptor. MOR174-9, a well-characterized receptor with a narrowly tuned MRR, did not respond to any novel compounds in our new panel. These results support the idea that variation in tuning breadth among these three ORs is not an artifact of the screening protocol, but is an intrinsic property of the receptors.
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