Structure of the human FOXO4-DBD-DNA complex at 1.9 A resolution reveals new details of FOXO binding to the DNA
Structure of the human FOXO4-DBD-DNA complex at 1.9 A resolution reveals new details of FOXO binding to the DNA
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DOI：
10.1107/s0907444910042228
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Obsil, Tomas
中科院分区：
文献类型：
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作者：
Boura, Evzen;Rezabkova, Lenka;Obsil, Tomas
FOXO4是叉头转录因子FOXO亚群的一员，叉头转录因子是连接生长和应激信号与转录控制的保守信号通路的关键组成部分。本文报道了人类FOXO4 DNA结合域（FOXO4- dbd）与含有FOXO一致结合序列的13 bp DNA双链结合的1.9 A分辨率晶体结构。该结构显示出与其他两种FOXO蛋白相似的核心序列识别。螺旋H3与主槽对接，提供所有碱基特异性接触，而n端和翼W1则与DNA的磷酸基进行额外接触。与其他FOXO-DBD-DNA结构不同，螺旋H2和H3之间的环具有不同的构象并参与DNA结合。此外，FOXO4-DBD-DNA复合物的结构表明，直接的水-DNA碱基接触和独特的水-网络相互作用都有助于FOXO-DBD以序列特异性的方式与DNA结合。
FOXO4 is a member of the FOXO subgroup of forkhead transcription factors that constitute key components of a conserved signalling pathway that connects growth and stress signals to transcriptional control. Here, the 1.9 A resolution crystal structure of the DNA-binding domain of human FOXO4 (FOXO4-DBD) bound to a 13 bp DNA duplex containing a FOXO consensus binding sequence is reported. The structure shows a similar recognition of the core sequence as has been shown for two other FOXO proteins. Helix H3 is docked into the major groove and provides all of the base-specific contacts, while the N-terminus and wing W1 make additional contacts with the phosphate groups of DNA. In contrast to other FOXO-DBD-DNA structures, the loop between helices H2 and H3 has a different conformation and participates in DNA binding. In addition, the structure of the FOXO4-DBD-DNA complex suggests that both direct water-DNA base contacts and the unique water-network interactions contribute to FOXO-DBD binding to the DNA in a sequence-specific manner.