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-Structure paper
タイトル | The structural basis of odorant recognition in insect olfactory receptors. |
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ジャーナル・号・ページ | Nature, Vol. 597, Issue 7874, Page 126-131, Year 2021 |
掲載日 | 2021年8月4日 |
著者 | Josefina Del Mármol / Mackenzie A Yedlin / Vanessa Ruta / |
PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:34349260 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 3.3 Å |
構造データ | EMDB-23372: The structure of the insect olfactory receptor OR5 from Machilis hrabei. EMDB-23374: The structure of the insect olfactory receptor OR5 from Machilis hrabei in complex with eugenol. EMDB-23375: The structure of the insect olfactory receptor OR5 from Machilis hrabei in complex with DEET. |
化合物 | ChemComp-EOL: ChemComp-DE3: |
由来 |
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キーワード | MEMBRANE PROTEIN / olfactory receptor / ion channel / eugenol / DEET |