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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Atomic force microscopy reveals the stoichiometry and subunit arrangement of 5-HT3 receptors
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Atomic force microscopy reveals the stoichiometry and subunit arrangement of 5-HT3 receptors

机译：原子力显微镜揭示5-HT3受体的化学计量和亚基排列

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摘要

The 5-HT3 receptor is a cation-selective ligand-gated ion channel of the Cys-loop superfamily. The receptor is an important therapeutic target, with receptor antagonists being widely used as antiemetics in cancer therapy. The two known receptor subunits, A and B, form homomeric 5-HT3A receptors and heteromeric 5-HT3A/B receptors. The heteromeric receptor has the higher single-channel conductance and more closely mimics the properties of the native receptor. We have used atomic force microscopy to study the architecture of 5-HT3A and 5-HT3A/B receptors. We engineered different epitope tags onto the A- and B-subunits and imaged receptors that were doubly liganded by anti-epitope antibodies. We found that, for the 5-HT3A/B receptor, the distribution of angles between antibodies against the A-subunit had a single peak at approximate to 144 degrees, whereas the distribution for antibodies against the B-subunit had two peaks at approximate to 72 degrees and 144 degrees. Our results indicate that the subunit stoichionnetry is 2A:3B and that the subunit arrangement around the receptor rosette is B-B-A-B-A. This arrangement may account for the difference between the agonist Hill coefficients and the single-channel conductances for the two types of receptor.
机译：5-HT3受体是Cys环超家族的阳离子选择性配体门控离子通道。受体是重要的治疗靶标，受体拮抗剂被广泛用作癌症治疗中的止吐药。两种已知的受体亚基A和B形成同型5-HT3A受体和异型5-HT3A / B受体。异聚受体具有更高的单通道电导率，并且更接近地模仿天然受体的特性。我们已经使用原子力显微镜来研究5-HT3A和5-HT3A / B受体的体系结构。我们将不同的抗原决定簇标签工程化到A和B亚基上，并成像了被抗表位抗体双重配体的受体。我们发现，对于5-HT3A / B受体，针对A亚基的抗体之间的角度分布在约144度处有一个峰，而针对B亚基的抗体的分布在约144度处有两个峰。 72度和144度。我们的结果表明亚化学计量是2A：3B，受体花环周围的亚单位排列是B-B-A-B-A。这种布置可以解释两种类型的受体的激动剂希尔系数和单通道电导之间的差异。

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