7LIG

The structure of the insect olfactory receptor OR5 from Machilis hrabei in complex with DEET

7LIG の概要

• エントリーDOI: 10.2210/pdb7lig/pdb
• EMDBエントリー: 23375
• 分子名称: MhOR5, N,N-diethyl-3-methylbenzamide (2 entities in total)
• 機能のキーワード: olfactory receptor, ion channel, membrane protein, deet
• 由来する生物種: Machilis hrabei
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 215711.86

構造登録者

del Marmol, J.,Ruta, V. (登録日: 2021-01-27, 公開日: 2021-08-11, 最終更新日: 2024-05-29)

主引用文献

Del Marmol, J.,Yedlin, M.A.,Ruta, V.
The structural basis of odorant recognition in insect olfactory receptors.
Nature, 597:126-131, 2021

PubMed Abstract: 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.

PubMed: 34349260
DOI: 10.1038/s41586-021-03794-8

実験手法

ELECTRON MICROSCOPY (2.9 Å)