Structure of the GCM domain-DNA complex:: a DNA-binding domain with a novel fold and mode of target site recognition
Structure of the GCM domain-DNA complex:: a DNA-binding domain with a novel fold and mode of target site recognition
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DOI：
10.1093/emboj/cdg182
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发表时间：
2003-04-15
期刊：
影响因子：
11.4
通讯作者：
Müller, CW
中科院分区：
文献类型：
--
作者：
Cohen, SX;Moulin, M;Müller, CW
胶质细胞缺失（GCM）转录因子在后生动物中形成了一个小的转录调节因子家族。果蝇的原型GCM蛋白指导神经元前体细胞向神经胶质细胞的分化，而哺乳动物的GCM蛋白则参与胎盘和甲状旁腺的发育。GCM蛋白共享一个高度保守的150个氨基酸残基区域，负责DNA结合，称为GCM结构域。在这里，我们以2.85埃的分辨率展示了小鼠GCMa结合其八聚体DNA靶点的GCM结构域的晶体结构。GCM结构域呈现出由两个结构Zn离子中的一个连接在一起的两个结构域组成的新褶皱。我们观察到β -片在DNA识别中的新用途，即五链β -片突出到垂直于DNA轴的主要凹槽中。该结构结合靶位点和DNA接触残基的突变分析，为这种新型含锌DNA结合结构域的DNA识别提供了新的见解。
Glia cell missing (GCM) transcription factors form a small family of transcriptional regulators in metazoans. The prototypical Drosophila GCM protein directs the differentiation of neuron precursor cells into glia cells, whereas mammalian GCM proteins are involved in placenta and parathyroid development. GCM proteins share a highly conserved 150 amino acid residue region responsible for DNA binding, known as the GCM domain. Here we present the crystal structure of the GCM domain from murine GCMa bound to its octameric DNA target site at 2.85 Angstrom resolution. The GCM domain exhibits a novel fold consisting of two domains tethered together by one of two structural Zn ions. We observe the novel use of a beta-sheet in DNA recognition, whereby a five- stranded beta-sheet protrudes into the major groove perpendicular to the DNA axis. The structure combined with mutational analysis of the target site and of DNA-contacting residues provides insight into DNA recognition by this new type of Zn-containing DNA-binding domain.