Conserved region I of human coactivator TAF4 binds to a short hydrophobic motif present in transcriptional regulators
Conserved region I of human coactivator TAF4 binds to a short hydrophobic motif present in transcriptional regulators
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DOI：
10.1073/pnas.0608570104
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发表时间：
2007-05-08
影响因子：
11.1
通讯作者：
Jacobson, Raymond H.
中科院分区：
文献类型：
--
作者：
Wang, Xiaoping;Truckses, Dagmar M.;Jacobson, Raymond H.
TBP 相关因子 4 (TAF4) 是 THID 复合物的重要亚基，可作为多种转录调节因子（包括 Sp1 和 CREB）的共激活因子。然而，对于导致共激活子功能的 TAF4 亚基的结构特性知之甚少。在这里，我们报告了人类 TAF4-TAFH 结构域的 2.0 埃分辨率晶体结构，该结构域是所有后生动物 TAK TAF4b 和 ETO 家族成员中的保守结构域。 hTAF4-TAFH结构采用完全螺旋折叠，具有大的疏水凹槽，形成TAF4相互作用因子的结合表面。使用肽噬菌体展示，我们表征了 hTAF4-TAFH 结构域对疏水基序 D Psi Psi xi xi Psi phi 的结合偏好，该基序存在于许多核因子中，包括几个在激活、抑制和调节翻译后修饰中发挥作用的重要转录调节因子。 hTAF4-TAFH 结构与同源 ETO-TAFH 结构域的比较揭示了几个对 hTAF4-TAFH 靶标特异性重要的关键残基，并表明 TAF4 的进化是为了响应后生动物转录复杂性的增加。
TBP-associated factor 4 (TAF4), an essential subunit of the THID complex acts as a coactivator for multiple transcriptional regulators, including Sp1 and CREB. However, little is known regarding the structural properties of the TAF4 subunit that lead to the coactivator function. Here, we report the crystal structure at 2.0-angstrom resolution of the human TAF4-TAFH domain, a conserved domain among all metazoan TAK TAF4b, and ETO family members. The hTAF4-TAFH structure adopts a completely helical fold with a large hydrophobic groove that forms a binding surface for TAF4 interacting factors. Using peptide phage display, we have characterized the binding preference of the hTAF4-TAFH domain for a hydrophobic motif, D Psi Psi xi xi Psi phi, that is present in a number of nuclear factors, including several important transcriptional regulators with roles in activating, repressing, and modulating posttranslational modifications. A comparison of the hTAF4-TAFH structure with the homologous ETO-TAFH domain reveals several critical residues important for hTAF4-TAFH target specificity and suggests that TAF4 has evolved in response to the increased transcriptional complexity of metazoans.