小柯机器人

2024年3月6日，美国耶鲁大学Joel A. Butterwick小组在《自然》杂志发表论文，揭示出昆虫味觉受体检测糖分的分子基础。

为了深入了解糖选择性的分子基础，研究人员测定了家蚕的味觉受体Gr9（BmGr9）在没有和有其唯一激活配体D-果糖的情况下的结构。这些结构以及结构诱导突变和功能测试说明了D-果糖是如何被一个配体结合口袋所包围的，该口袋与D-果糖中化学基团的整体形状和模式精确匹配。然而，计算对接和实验结合分析表明，其他糖类也能与BmGr9结合，但却无法激活受体。研究人员确定了BmGr9与其中一种非激活糖（L-山梨糖）的复合结构。

虽然这两种糖的结合位置相似，但只有D-果糖能够与连接口袋和孔螺旋的两个保守芳香残基桥接，从而引起构象变化，使离子传导孔打开。因此，化学特异性并不完全取决于配体结合口袋的选择性，而是受体-配体相互作用和异构耦合共同作用的结果。这些研究结果支持这样一个模型，即受体的粗调来自于口袋的大小和化学特性，而受体激活的微调则通过调节离子传导的异构途径的选择性参与来实现。

研究人员表示，动物之所以渴求糖类，是因为它们具有潜在的能量和品尝甜味的愉悦感。然而，并非所有的糖在代谢上都是等同的，这就需要有机制来检测和区分化学性质相似的甜味物质。昆虫利用一系列离子味觉受体来区分糖类，每种受体都会被特定的甜味分子选择性地激活。

附：英文原文

Title: The molecular basis of sugar detection by an insect taste receptor

Author: Gomes, Joo Victor T., Singh-Bhagania, Shivinder, Cenci, Matthew, Cordon, Carlos Chacon, Singh, Manjodh, Butterwick, Joel A.

Issue&Volume: 2024-03-06

Abstract: Animals crave sugars because of their energy potential and the pleasurable sensation of tasting sweetness. Yet all sugars are not metabolically equivalent, requiring mechanisms to detect and differentiate between chemically similar sweet substances. Insects use a family of ionotropic gustatory receptors to discriminate sugars1, each of which is selectively activated by specific sweet molecules2–6. To gain insight into the molecular basis of sugar selectivity, we determined structures of Gr9, a gustatory receptor from the silkworm Bombyx mori (BmGr9), in the absence and presence of its sole activating ligand, D-fructose. These structures, along with structure-guided mutagenesis and functional assays, illustrate how D-fructose is enveloped by a ligand-binding pocket that precisely matches the overall shape and pattern of chemical groups in D-fructose. However, our computational docking and experimental binding assays revealed that other sugars also bind BmGr9, yet they are unable to activate the receptor. We determined the structure of BmGr9 in complex with one such non-activating sugar, L-sorbose. While both sugars bind a similar position, only D-fructose is capable of engaging a bridge of two conserved aromatic residues that connects the pocket to the pore helix, inducing a conformational change that allows the ion-conducting pore to open. Thus, chemical specificity does not depend solely on the selectivity of the ligand-binding pocket, but it is an emergent property arising from a combination of receptor-ligand interactions and allosteric coupling. Our results support a model whereby coarse receptor tuning is derived from the size and chemical characteristics of the pocket, whereas fine-tuning of receptor activation is achieved through the selective engagement of an allosteric pathway that regulates ion conduction.

DOI: 10.1038/s41586-024-07255-w

Source: https://www.nature.com/articles/s41586-024-07255-w

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