人甜味受体亚基T1R2和T1R3对葡萄糖对映体激活的敏感性。

IF 2.8 4区 心理学 Q1 BEHAVIORAL SCIENCES Chemical Senses Pub Date : 2023-01-01 DOI:10.1093/chemse/bjad005
Nitzan Dubovski, Yaron Ben-Shoshan Galezcki, Einav Malach, Masha Y Niv
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引用次数: 0

摘要

我们之前已经证明,l-葡萄糖,d-葡萄糖的无热量对映体,激活HEK293T细胞中短暂表达的人类甜味受体T1R2/T1R3。在这里,我们发现d-葡萄糖和l-葡萄糖也可以激活没有对应单体的T1R2和T1R3表达。T1R3 VFT结构域结合位点147残基上的丙氨酸发生丝氨酸突变,完全消除了l-或d-葡萄糖对T1R3S147A的激活,而T1R2/T1R3S147A的反应与没有对应物的T1R2相同。我们进一步表明,原始的T1R2参考序列(NM_152232.1)比进行本研究时的参考序列(NM_152232.4)敏感度低了几乎一个数量级。我们发现,在四个不同的位置中,是T1R2的VFT结构域的R317G在体外产生了这种作用。这对于实际的测定灵敏度和甘氨酸在世界人口中约20%的位置都是重要的。虽然突变和部分转染对d和l对映体的影响相似,但它们的剂量-反应曲线仍然不同,l-葡萄糖达到早期平台。
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Sensitivity of human sweet taste receptor subunits T1R2 and T1R3 to activation by glucose enantiomers.

We have previously shown that l-glucose, the non-caloric enantiomer of d-glucose, activates the human sweet taste receptor T1R2/T1R3 transiently expressed in HEK293T cells. Here, we show that d- and l-glucose can also activate T1R2 and T1R3 expressed without the counterpart monomer. Serine mutation to alanine in residue 147 in the binding site of T1R3 VFT domain, completely abolishes T1R3S147A activation by either l- or d-glucose, while T1R2/T1R3S147A responds in the same way as T1R2 expressed without its counterpart. We further show that the original T1R2 reference sequence (NM_152232.1) is less sensitive by almost an order of magnitude than the reference sequence at the time this study was performed (NM_152232.4). We find that out of the four differing positions, it is the R317G in the VFT domain of T1R2, that is responsible for this effect in vitro. It is significant for both practical assay sensitivity and because glycine is found in this position in ~20% of the world population. While the effects of the mutations and the partial transfections were similar for d and l enantiomers, their dose-response curves remained distinct, with l-glucose reaching an early plateau.

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来源期刊
Chemical Senses
Chemical Senses 医学-行为科学
CiteScore
8.60
自引率
2.90%
发文量
25
审稿时长
1 months
期刊介绍: Chemical Senses publishes original research and review papers on all aspects of chemoreception in both humans and animals. An important part of the journal''s coverage is devoted to techniques and the development and application of new methods for investigating chemoreception and chemosensory structures.
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