Starich M R, Wikström M, Arst H N, Clore G M, Gronenborn A M
National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
J Mol Biol. 1998 Apr 3;277(3):605-20. doi: 10.1006/jmbi.1998.1625.
The solution structure of a complex between the DNA binding domain of a fungal GATA factor and a 13 base-pair oligonucleotide containing its physiologically relevant CGATAG target sequence has been determined by multidimensional nuclear magnetic resonance spectroscopy. The AREA DNA binding domain, from Aspergillus nidulans, possesses a single Cys2-Cys2 zinc finger module and a basic C-terminal tail, which recognize the CGATAG element via an extensive network of hydrophobic interactions with the bases in the major groove and numerous non-specific contacts along the sugar-phosphate backbone. The zinc finger core of the AREA DNA binding domain has the same global fold as that of the C-terminal DNA binding domain of chicken GATA-1. In contrast to the complex with the DNA binding domain of GATA-1 in which the basic C-terminal tail wraps around the DNA and lies in the minor groove, the structure of complex with the AREA DNA binding domain reveals that the C-terminal tail of the fungal domain runs parallel with the sugar phosphate backbone along the edge of the minor groove. This difference is principally attributed to amino acid substitutions at two positions of the AREA DNA binding domain (Val55, Asn62) relative to that of GATA-1 (Gly55, Lys62). The impact of the different C-terminal tail binding modes on the affinity and specificity of GATA factors is discussed.
通过多维核磁共振光谱法，已确定一种真菌GATA因子的DNA结合结构域与一个包含其生理相关CGATAG靶序列的13个碱基对寡核苷酸之间复合物的溶液结构。来自构巢曲霉的AREA DNA结合结构域具有单个Cys2-Cys2锌指模块和一个碱性C末端尾巴，其通过与大沟中碱基的广泛疏水相互作用网络以及沿糖-磷酸骨架的众多非特异性接触来识别CGATAG元件。AREA DNA结合结构域的锌指核心与鸡GATA-1的C末端DNA结合结构域具有相同的整体折叠。与GATA-1的DNA结合结构域形成的复合物中碱性C末端尾巴环绕DNA并位于小沟不同，与AREA DNA结合结构域形成的复合物结构显示，真菌结构域的C末端尾巴沿着小沟边缘与糖磷酸骨架平行。这种差异主要归因于AREA DNA结合结构域相对于GATA-1（Gly55，Lys62）在两个位置（Val55，Asn62）的氨基酸取代。讨论了不同C末端尾巴结合模式对GATA因子亲和力和特异性的影响。
