Conformational changes of the glucocorticoid receptor ligand binding domain induced by ligand and cofactor binding, and the location of cofactor binding sites determined by hydrogen/deuterium exchange mass spectrometry
Conformational changes of the glucocorticoid receptor ligand binding domain induced by ligand and cofactor binding, and the location of cofactor binding sites determined by hydrogen/deuterium exchange mass spectrometry
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DOI：
10.1110/ps.051781406
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发表时间：
2006-04-01
期刊：
影响因子：
8
通讯作者：
Davidson, W
中科院分区：
文献类型：
--
作者：
Frego, L;Davidson, W
描述了与激动剂地塞米松和拮抗剂 RU-486 复合的糖皮质激素受体配体结合结构域 (GR LBD) 的 HXMS（氢/氘交换质谱）。与 GR 地塞米松复合物相比，在与已发表的 GR LBD 与 RU-486 复合物的晶体结构一致的区域中观察到交换速率的变化。我们还报告了具有共激活因子转录中间因子 2 (TIF2) 的激动剂结合 GR LBD 和具有核受体辅阻遏物 (NCoR) 的拮抗剂结合 GR LBD 的 HXMS 结果。观察到存在 TIF2 的激动剂结合 GR LBD 的交换率变化与已发表的复合物晶体结构接触一致。观察到的拮抗剂结合的 GR LBD 与 NCoR 的交换率变化是 TIF2 结合观察到的交换率的改变的一个子集，表明共激活剂和辅阻遏物有共同或重叠的结合位点。
HXMS (hydrogen/deuterium exchange mass spectrometry) of the glucocorticoid receptor ligand-binding domain (GR LBD) complexed with the agonist dexamethasone and the antagonist RU-486 is described. Variations in the rates of exchange were observed in regions consistent with the published crystal structures of GR LBD complexed with RU-486 when compared with the GR dexamethasone complex. We also report the HXMS results for agonist-bound GR LBD with the coactivator transcriptional intermediary factor 2 (TIF2) and anatagonist-bound GR LBD with nuclear receptor corepressor ( NCoR). Alterations in exchange rates observed for agonist-bound GR LBD with TIF2 present were consistent with the published crystal structural contacts for the complex. Alterations in exchange rates observed for antagonist-bound GR LBD with NCoR were a subset of those observed with TIF2 binding, suggesting a common or overlapping binding site for coactivator and corepressor.