Crystal structures of multiple GATA zinc fingers bound to DNA reveal new insights into DNA recognition and self-association by GATA.
Crystal structures of multiple GATA zinc fingers bound to DNA reveal new insights into DNA recognition and self-association by GATA.
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DOI：
10.1016/j.jmb.2008.06.072
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发表时间：
2008-09-19
影响因子：
5.6
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Bates DL;Chen Y;Kim G;Guo L;Chen L
GATA转录因子家族(GATA1-6)结合脊椎动物基因组中特定的GATA位点来调节特定基因的表达。尽管脊椎动物GATA因子有两个高度保守的锌指基序，但这两个手指如何共同作用识别功能DNA元件尚不清楚。在这里，我们测定了小鼠GATA3与DNA结合的C-末端锌指(C-Finger)的晶体结构，其中包含两个不同排列的GATA结合位点。我们的结构和伴随的生化分析揭示了GATA与紧密排列的位点结合的两种不同的DNA模式。一种模式涉及两个GATA因子的协同结合，这两个因子通过蛋白质-蛋白质相互作用相互作用。另一种涉及同一GATA因子的N-末端锌指(N-Finger)和C-指的同时结合。我们的研究是首次对GATA锌指与DNA结合的结晶学分析，并为GATA锌指识别DNA的机制提供了新的见解。我们的晶体结构还揭示了GATA中的二聚化界面，这一界面先前已被证明对GATA自结合是重要的。这些发现极大地促进了我们对GATA结构和功能的理解，并为进一步研究GATA依赖的基因调控的体内机制提供了重要的框架。
The GATA family of transcription factors (GATA1–6) binds selected GATA sites in vertebrate genomes to regulate specific gene expression. Although vertebrate GATA factors have two highly conserved zinc finger motifs, how the two fingers act together to recognize functional DNA elements is not well understood. Here we determined the crystal structures of the C-terminal zinc finger (C-finger) of mouse GATA3 bound to DNA containing two variously arranged GATA-binding sites. Our structures and accompanying biochemical analyses reveal two distinct modes of DNA binding by GATA to closely arranged sites. One mode involves cooperative binding by two GATA factors that interact with each other through protein-protein interactions. The other involves simultaneous binding of the N-terminal zinc finger (N-finger) and C-finger of the same GATA factor. Our studies represent the first crystallographic analysis of GATA zinc fingers bound to DNA and provide new insights into the DNA recognition mechanism by the GATA zinc finger. Our crystal structure also reveals a dimerization interface in GATA that has previously been shown to be important for GATA self-association. These findings significantly advance our understanding of the structure and function of GATA and provide an important framework for further investigating the in vivo mechanisms GATA-dependent gene regulation.