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首页> 外文期刊>Biochemistry >The Mouse Eugenol Odorant Receptor: Structural and Functional Plasticity of a Broadly Tuned Odorant Binding Pocket
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The Mouse Eugenol Odorant Receptor: Structural and Functional Plasticity of a Broadly Tuned Odorant Binding Pocket

机译：小鼠丁香酚气味受体：结构和功能可塑性的广泛调整气味气味的绑定口袋。

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Molecular interactions of odorants with their olfactory receptors (ORs) are of central importance for the ability of the mammalian olfactory system to detect and discriminate a vast variety of odors with a limited set of receptors. How a particular OR binds and distinguishes different odorant molecules remains largely unknown on a structural basis. Here we investigated this question for the mouse eugenol receptor (mOR-EG). By screening a large odorant library, we discovered a wDEe range of chemical structures activating the receptor in heterologous mammalian cells. Potent agonists comprise (i) benzene, (ii) cyclohexane, or (iii) polycyclic structures substituted with alcohol, aldehyde, keto, ether, or esterified carboxylic groups. To detect those amino acDEs within the receptor that are in contact with a particular bound odorant molecule, we investigated how distinct mOR-EG point mutants were activated by the different odorant agonists found for the wild-type receptor. We DEentified 11 amino acDEs as a part of the receptor's ligand binding pocket. Molecular modeling predicted 10 of these resDEues in transmembrane helices TM3-TM6 and one in the extracellular loop between TM2 and TM3. These amino acDEs participate in odorant binding with variable importance depending on the type of odorant, revealing functional "fingerprints" of ligand-receptor interactions.
机译：气味剂与它们的嗅觉受体（OR）的分子相互作用对于哺乳动物嗅觉系统检测和辨别种类有限的受体的多种气味的能力至关重要。在结构上，特定的OR如何结合和区分不同的气味分子仍是未知之数。在这里，我们调查了小鼠丁子香酚受体（mOR-EG）的问题。通过筛选大型的气味库，我们发现了wDEe范围的化学结构，可激活异源哺乳动物细胞中的受体。有效的激动剂包括（i）苯，（ii）环己烷或（iii）被醇，醛，酮，醚或酯化的羧基取代的多环结构。为了检测受体中与特定结合的气味分子接触的氨基acDE，我们研究了野生型受体的不同气味激动剂如何激活不同的mOR-EG点突变体。我们确定11种氨基acDEs作为受体配体结合口袋的一部分。分子模型预测跨膜螺旋TM3-TM6中有10种这些残基，而TM2和TM3之间的细胞外环中则有一种。这些氨基acDEs取决于气味的类型而以不同的重要性参与气味的结合，从而揭示了配体-受体相互作用的功能“指纹”。

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