An Aryl Hydrocarbon Receptor from the Salamander Ambystoma mexicanum Exhibits Low Sensitivity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin.
An Aryl Hydrocarbon Receptor from the Salamander Ambystoma mexicanum Exhibits Low Sensitivity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin.
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DOI：
10.1021/acs.est.5b01299
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发表时间：
2015-06-02
影响因子：
11.4
通讯作者：
Powell, Wade H.
中科院分区：
文献类型：
--
作者：
Shoots, Jenny;Fraccalvieri, Domenico;Franks, Diana G.;Denison, Michael S.;Hahn, Mark E.;Bonati, Laura;Powell, Wade H.
芳烃受体（AHR）的结构特征可以解释其对2，3，7，8-四氯二苯并-对-二恶英（TCDD）亲和力的物种和种群特异性差异。这些差异通常解释了TCDD毒性的差异。青蛙对二恶英相对不敏感，爪蟾AHR与TCDD的结合亲和力较低。弱TCDD结合是由配体结合结构域中的三个残基：A354和A370以及N325的组合产生的。在这里，我们试图确定这种机制的弱TCDD结合是否是由其他两栖动物AHR共享。我们从墨西哥蝾螈（Ambystoma mexicanum）中分离了AHR cDNA。所编码的多肽在赋予X低TCDD亲和力的位置处含有相同的残基。Iaevis AHR（A364、A380和N335），并且同源性建模预测它们突出到结合腔中。在速度沉降分析中，蝾螈AHR结合的TCDD是小鼠AHR的十分之一，在反式激活试验中，TCDD的EC 50为23 nM，与X相似。Iaevis AHR 1 β（27 nM），大于含有小鼠配体结合结构域的AHR（0.08 nM）。序列、结构模型和功能表明美西螈AHR与TCDD结合较弱，预测美西螈AHR与TCDD结合较弱。mexicanum对TCDD毒性缺乏敏感性。我们假设，这一特点的蝾螈和非洲爪蟾AHRs出现在一个共同的祖先的有尾类和无尾类。
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 N335), 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 EC50 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 to TCDD toxicity. We hypothesize that this characteristic of axolotl and Xenopus AHRs arose in a common ancestor of the Caudata and Anura.
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DOI：
10.1016/0272-0590(90)90175-j
发表时间：
1990-07-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
BIRNBAUM, LS;MCDONALD, MM;HARRIS, MW
通讯作者：
HARRIS, MW
影响因子：
5.1
作者：
Farmahin, Reza;Crump, Doug;Kennedy, Sean W.
通讯作者：
Kennedy, Sean W.
影响因子：
5.7
作者：
Anderson, CAF;Palmer, AG;Rost, B
通讯作者：
Rost, B
影响因子：
5.9
作者：
Contreras, Victoria;Martinez-Meyer, Enrique;Zambrano, Luis
通讯作者：
Zambrano, Luis
影响因子：
6.9
作者：
Gresens, J
通讯作者：
Gresens, J