Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α
Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α
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DOI：
10.1073/pnas.082117899
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发表时间：
2002-04-16
影响因子：
11.1
通讯作者：
Eck, MJ
中科院分区：
文献类型：
--
作者：
Freedman, SJ;Sun, ZYJ;Eck, MJ
对缺氧的适应是由缺氧诱导因子-1 （HIF-1）与CBP和p300转录共激活因子复合物对缺氧反应基因的反激活介导的。我们报道了p300的富含半胱氨酸/组氨酸的1 （CH1）结构域与HIF-1alpha的c端转激活结构域结合的溶液结构。CH1具有由四个a-螺旋和三个Zn2+配位中心组成的三角形几何结构。CH1作为HIF-1alpha c端反激活结构域折叠的支架，在CH1结构域上形成一个钳子状的钳子，通过广泛的疏水和极性相互作用来稳定CH1结构域。该结构揭示了HIF-1alpha特异性识别p300的机制，并显示了HIF-1alpha如何通过天冬酰胺羟基化调节转激活。
Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators. We report the solution structure of the cysteine/histidine-rich 1 (CH1) domain of p300 bound to the C-terminal transactivation domain of HIF-1alpha. CH1 has a triangular geometry composed of four a-helices with three intervening Zn2+-coordinating centers. CH1 serves as a scaffold for folding of the HIF-1alpha C-terminal transactivation domain, which forms a vise-like clamp on the CH1 domain that is stabilized by extensive hydrophobic and polar interactions. The structure reveals the mechanism of specific recognition of p300 by HIF-1alpha, and shows how HIF-1alpha transactivation is regulated by asparagine hydroxylation.