Structural model for ligand binding and channel opening of an insect gustatory receptor.
Structural model for ligand binding and channel opening of an insect gustatory receptor.
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DOI：
10.1016/j.jbc.2022.102573
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发表时间：
2022-11
影响因子：
4.8
通讯作者：
Touhara, Kazushige
中科院分区：
文献类型：
--
作者：
Morinaga, Satoshi;Nagata, Koji;Ihara, Sayoko;Yumita, Tomohiro;Niimura, Yoshihito;Sato, Koji;Touhara, Kazushige
昆虫的味觉感受器在感知诸如糖和苦味物质等味觉物质方面发挥作用。我们之前证明了BmGr9家蚕味觉受体是一种d-果糖门控离子通道受体。然而，d-果糖如何启动通道打开的分子机制尚不清楚。在此，我们提出了BmGr9的通道孔和d-果糖结合位点的结构模型。由于BmGr9的膜拓扑结构和寡聚态与昆虫气味受体的协同受体Orco相似，我们基于冷冻电镜Orco结构构建了BmGr9的结构模型。我们的定点诱变数据表明，跨膜区7形成通道孔并控制通道门控。该模型还表明，由跨膜螺旋2至4和6形成的口袋结合了d-果糖。利用诱变实验结合对接模拟，我们能够确定d-果糖的有效结合模式。最后，基于这些数据，我们提出了一种构象变化，导致d-果糖结合时通道打开。综上所述，这些发现详细说明了昆虫味觉受体被其配体分子激活的分子机制。
Insect gustatory receptors play roles in sensing tastants, such as sugars and bitter substances. We previously demonstrated that the BmGr9 silkworm gustatory receptor is a d-fructose–gated ion channel receptor. However, the molecular mechanism of how d-fructose could initiate channel opening were unclear. Herein, we present a structural model for a channel pore and a d-fructose–binding site in BmGr9. Since the membrane topology and oligomeric state of BmGr9 appeared to be similar to those of an insect odorant receptor coreceptor, Orco, we constructed a structural model of BmGr9 based on the cryo-EM Orco structure. Our site-directed mutagenesis data suggested that the transmembrane region 7 forms channel pore and controls channel gating. This model also suggested that a pocket formed by transmembrane helices 2 to 4 and 6 binds d-fructose. Using mutagenesis experiments in combination with docking simulations, we were able to determine the potent binding mode of d-fructose. Finally, based on these data, we propose a conformational change that leads to channel opening upon d-fructose binding. Taken together, these findings detail the molecular mechanism by which an insect gustatory receptor can be activated by its ligand molecule.
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影响因子：
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影响因子：
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作者：
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