TRANSCRIPTIONAL ACTIVATION BY THE ESTROGEN-RECEPTOR REQUIRES A CONFORMATIONAL CHANGE IN THE LIGAND-BINDING DOMAIN
TRANSCRIPTIONAL ACTIVATION BY THE ESTROGEN-RECEPTOR REQUIRES A CONFORMATIONAL CHANGE IN THE LIGAND-BINDING DOMAIN
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DOI：
10.1210/me.7.10.1266
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发表时间：
1993-10-01
影响因子：
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通讯作者：
OMALLEY, BW
中科院分区：
文献类型：
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作者：
BEEKMAN, JM;ALLAN, GF;OMALLEY, BW
雌激素受体（ER）是一种强的雌激素诱导转录因子，调节许多基因的表达。对于人孕酮受体，显示激素的结合导致配体结合结构域（LBD）中的不同构象变化，并且LBD构象中的这些变化对于DNA结合后的事件是至关重要的。我们现在表明，在LBD的人ER的构象变化是一个先决条件的反式激活。在适当的条件下，ER与其反应元件结合，仅在配体存在下激活转录。配体的结合引起LBD构象的变化。抗激素诱导不同的构象变化，构象之间的差异在于受体的羧基末端。改变实验条件会产生一种可以与DNA结合并以配体非依赖性方式激活转录的受体。在这些条件下，LBD在不存在配体的情况下具有转录活性构象。两者合计，我们的数据表明，由配体诱导的构象变化是需要转换受体的转录活性形式。
The estrogen receptor (ER) is a strong hormone-inducible transcription factor that regulates the expression of many genes. It was shown for the human progesterone receptor that the binding of hormone causes distinct conformational changes in the ligand binding domain (LBD) and that these changes in LBD conformation are crucial for events after DNA binding. We now show that conformational changes in the LBD of the human ER are a prerequisite for trans-activation. Under the appropriate conditions ER binds to its response element and activates transcription only in the presence of ligand. Binding of the ligand causes changes in the conformation of the LBD. Antihormones induce distinct conformational changes, the differences between the conformations lying in the carboxy-terminal end of the receptor. Changing the experimental conditions results in a receptor that can bind to DNA and activate transcription in a ligand-independent manner. Under these conditions the LBD has a transcriptionally active conformation in the absence of ligand. Taken together, our data indicate that the conformational change induced by ligand is required for converting a receptor to the transcriptionally active form.