Structural insights into cooperative DNA recognition by the CCAAT-binding complex and its bZIP transcription factor HapX
Structural insights into cooperative DNA recognition by the CCAAT-binding complex and its bZIP transcription factor HapX
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DOI：
10.1016/j.str.2022.04.001
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发表时间：
2022-07-07
期刊：
影响因子：
5.7
通讯作者：
Groll, Michael
中科院分区：
文献类型：
--
作者：
Huber, Eva M.;Hortschansky, Peter;Groll, Michael
异源三聚体CCAAT结合复合物（CBC）是一种重要的真核转录因子，它能使CCAAT盒内的CCAAT盒蛋白表达增加。在某些真菌中，如黑曲霉，CBC与碱性亮氨酸拉链HapX合作控制铁代谢。HapX在功能上依赖于CBC，两者的稳定相互作用需要DNA。为了研究这种协同效应，测定CBC-HapX-DNA复合物的X射线结构。在CBC占据的CCAAT盒的下游，HapX二聚体与大沟结合。远端HapX亚基的皮带样N末端接触CBC，并通过一个灵活的聚脯氨酸II型螺旋介导小沟相互作用，刺激序列混杂。体外和体内诱变表明，HapX的结构和功能可塑性是由局部不对称性及其同时靶向大沟和小沟的能力引起的。后一特征也可应用于相关转录因子，例如酵母Hap 4和不同的雅普家族成员。
The heterotrimeric CCAAT-binding complex (CBC) is a fundamental eukaryotic transcription factor recog-nizing the CCAAT box. In certain fungi, like Aspergilli, the CBC cooperates with the basic leucine zipper HapX to control iron metabolism. HapX functionally depends on the CBC, and the stable interaction of both requires DNA. To study this cooperative effect, X-ray structures of the CBC-HapX-DNA complex were determined. Downstream of the CCAAT box, occupied by the CBC, a HapX dimer binds to the major groove. The leash-like N terminus of the distal HapX subunit contacts the CBC, and via a flexible polyproline type II helix mediates minor groove interactions that stimulate sequence promiscuity. In vitro and in vivo mutagenesis suggest that the structural and functional plasticity of HapX results from local asymmetry and its ability to target major and minor grooves simultaneously. The latter feature may also apply to related transcription factors such as yeast Hap4 and distinct Yap family members.