Expression, purification and crystallization of the ancestral androgen receptor-DHT complex.
Expression, purification and crystallization of the ancestral androgen receptor-DHT complex.
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祖先雄激素受体-DHT 复合物的表达、纯化和结晶。
DOI：
10.1107/s1744309113018745
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Ortlund,EricA
中科院分区：
文献类型：
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作者：
Colucci,JenniferK;Ortlund,EricA
类固醇受体（SRs）是一个密切相关的配体依赖核受体家族，介导对发育、生殖和免疫至关重要的基因转录。SR失调与癌症、炎症性疾病和代谢紊乱有关。SRs结合其同源激素配体具有精细的特异性，为研究分子识别的进化提供了一个独特的系统。SR家族从一个对雌激素敏感的祖先进化而来，并分化为对孕激素、皮质激素和最近的雄激素敏感。为了了解驱动雄激素反应进化的结构机制，我们将祖先的雄激素受体（ancAR1）与5α-二氢睾酮（DHT）和转录介质/中介因子2 （Tif2）片段结合结晶。晶体衍射到2.1 Å分辨率，所得结构将允许与其孕激素敏感的祖先，祖先类固醇受体2 （AncSR2）进行直接比较。
Steroid receptors (SRs) are a closely related family of ligand-dependent nuclear receptors that mediate the transcription of genes critical for development, reproduction and immunity. SR dysregulation has been implicated in cancer, inflammatory diseases and metabolic disorders. SRs bind their cognate hormone ligand with exquisite specificity, offering a unique system to study the evolution of molecular recognition. The SR family evolved from an estrogen-sensitive ancestor and diverged to become sensitive to progestagens, corticoids and, most recently, androgens. To understand the structural mechanisms driving the evolution of androgen responsiveness, the ancestral androgen receptor (ancAR1) was crystallized in complex with 5α-dihydrotestosterone (DHT) and a fragment of the transcriptional mediator/intermediary factor 2 (Tif2). Crystals diffracted to 2.1 Å resolution and the resulting structure will permit a direct comparison with its progestagen-sensitive ancestor, ancestral steroid receptor 2 (AncSR2).