3D model of amphioxus steroid receptor complexed with estradiol

被引:13
作者
Baker, Michael E. [1 ]
Chang, David J. [2 ]
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA
关键词
Amphioxus steroid receptor; Steroid receptor evolution; Estrogen signaling; ESTROGEN-RECEPTOR; LIGAND-BINDING; NUCLEAR RECEPTOR; MINERALOCORTICOID RECEPTOR; PETROMYZON-MARINUS; CRYSTAL-STRUCTURE; SEX STEROIDS; EVOLUTION; SPECIFICITY; MECHANISMS;
D O I
10.1016/j.bbrc.2009.06.079
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER(x are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER alpha in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors. (C) 2009 Elsevier Inc. All rights reserved,
引用
收藏
页码:516 / 520
页数:5
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