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首页> 外文期刊>Environmental Science & Technology >An Aryl Hydrocarbon Receptor from the Salamander Ambystoma mexicanum Exhibits Low Sensitivity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin
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An Aryl Hydrocarbon Receptor from the Salamander Ambystoma mexicanum Exhibits Low Sensitivity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

机译：来自墨西哥Am的芳烃受体表现出对2,3,7,8-四氯二苯并-p-二恶英的低敏感性

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摘要

Structural features of the aryl hydrocarbon receptor (AHR) can underlie species- and population-specific differences in its affinity for 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD). These differences often explain variations in TCDD toxicity. Frogs are relatively insensitive to dioxin, and Xenopus AHRs bind TCDD with low affinity. Weak TCDD binding results from the combination of three residues in the ligand-binding domain: A354 and A370, and N325. Here we sought to determine whether this mechanism of weak TCDD binding is shared by other amphibian AHRs. We isolated an AHR cDNA from the Mexican axolotl {Ambystoma mexicanum). The encoded polypeptide contains identical residues at positions that confer low TCDD affinity to X. laevis AHRs (A364, A380, and N33S), and homology modeling predicts they protrude into the binding cavity. Axolotl AHR bound one-tenth the TCDD of mouse AHR in velocity sedimentation analysis, and in transactivation assays, the EC_(50) for TCDD was 23 nM, similar to X. laevis AHR1β (27 nM) and greater than AHR containing the mouse ligand-binding domain (0.08 nM). Sequence, modeled structure, and function indicate that axolotl AHR binds TCDD weakly, predicting that A. mexicanum lacks sensitivity toTCDD toxicity. We hypothesize that this characteristic of axolotl and Xenopus AHRs arose in a common ancestor of the Caudata and Anura.
机译：芳烃受体（AHR）的结构特征可归因于其对2,3,7,8-四氯二苯并二恶英（TCDD）的亲和力的物种和种群特异性差异。这些差异通常可以解释TCDD毒性的变化。青蛙对二恶英相对不敏感，非洲爪蟾AHR以低亲和力结合TCDD。弱的TCDD结合是由于配体结合域中三个残基的结合：A354和A370，以及N325。在这里，我们试图确定这种弱TCDD绑定机制是否被其他两栖动物AHR共享。我们从墨西哥a（Ambystoma mexicanum）中分离出AHR cDNA。编码的多肽在赋予X. laevis AHRs（A364，A380和N33S）低TCDD亲和力的位置含有相同的残基，同源性模型预测它们会突出到结合腔中。在速度沉降分析中，Axolotl AHR结合了小鼠AHR的TCDD的十分之一，而在反转录激活测定中，TCDD的EC_（50）为23 nM，类似于X. laevisAHR1β（27 nM），大于包含小鼠配体的AHR -结合域（0.08 nM）。序列，建模的结构和功能表明，Axolotl AHR与TCDD的结合较弱，这表明墨西哥曲霉对TCDD毒性缺乏敏感性。我们假设a虫和非洲爪蟾AHRs的这一特征起源于Caudata和Anura的共同祖先。

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  • 来源
    《Environmental Science & Technology》 |2015年第11期|6993-7001|共9页
  • 作者

    Jenny Shoots; Domenico Fraccalvieri; Diana G. Franks; Michael S. Denison; Mark E. Hahn; Laura Bonati; Wade H. Powell;

  • 作者单位

    Biology Department, Kenyon College, Gambier, Ohio 43022, United States ,Department of Pharmacology Weill Cornell Medical College New York, NY 10021 U.S.A.;

    Department of Earth and Environmental Sciences, University of Milano-Bicocca, 20126 Milan, Italy;

    Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02S43, United States;

    Department of Environmental Toxicology, University of California-Davis, Davis, California 95616, United States;

    Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02S43, United States;

    Department of Earth and Environmental Sciences, University of Milano-Bicocca, 20126 Milan, Italy;

    Biology Department, Kenyon College, Gambier, Ohio 43022, United States;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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