The structural basis of odorant recognition in insect olfactory receptors.
The structural basis of odorant recognition in insect olfactory receptors.
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DOI：
10.1038/s41586-021-03794-8
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发表时间：
2021-09
期刊：
影响因子：
64.8
通讯作者：
Ruta V
中科院分区：
文献类型：
--
作者：
Del Mármol J;Yedlin MA;Ruta V
嗅觉系统必须检测和区分各种各样的气味。为了应对这一挑战，不同的物种已经聚集在一个共同的策略，其中气味的身份是通过嗅觉受体的大家族的组合激活编码，从而允许有限数量的受体检测到一个巨大的化学世界。在这里，我们提供了结构和机制的见解如何个人的嗅觉受体可以灵活地识别不同的气味。我们发现，嗅觉受体MHOR5从跳跃的刺毛楠hrabei组装作为一个homotetrameric气味门控离子通道与广泛的化学调谐。使用冷冻电子显微镜，我们阐明了MHOR5的结构在多个门控状态，单独和复杂的两个激动剂的气味丁香酚和驱虫避蚊胺。这两种配体通过分布在相同的几何简单的结合口袋位于每个亚基的跨膜区域内的疏水相互作用来识别，这表明该受体的混杂化学敏感性的结构逻辑。可预见的是，排列在结合口袋中的单个残基的突变改变了MhOR 5对丁香酚和避蚊胺的敏感性，并广泛地重新配置了受体的调谐。总之，我们的数据支持一个模型，其中不同的气味具有相同的结构决定因素的结合，揭示了分子识别机制，最终赋予嗅觉系统的巨大的歧视能力。昆虫嗅觉受体的结构和功能分析揭示了受体如何被不同的气味激活。
Olfactory systems must detect and discriminate amongst an enormous variety of odorants. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors, thus allowing a finite number of receptors to detect a vast chemical world. Here we offer structural and mechanistic insight into how an individual olfactory receptor can flexibly recognize diverse odorants. We show that the olfactory receptor MhOR5 from the jumping bristletail Machilis hrabei assembles as a homotetrameric odorant-gated ion channel with broad chemical tuning. Using cryo-electron microscopy, we elucidated the structure of MhOR5 in multiple gating states, alone and in complex with two of its agonists—the odorant eugenol and the insect repellent DEET. Both ligands are recognized through distributed hydrophobic interactions within the same geometrically simple binding pocket located in the transmembrane region of each subunit, suggesting a structural logic for the promiscuous chemical sensitivity of this receptor. Mutation of individual residues lining the binding pocket predictably altered the sensitivity of MhOR5 to eugenol and DEET and broadly reconfigured the receptor’s tuning. Together, our data support a model in which diverse odorants share the same structural determinants for binding, shedding light on the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity. Structural and functional analysis of an insect olfactory receptor shed light on how receptors can be activated by diverse odorants.