GCM结构域-DNA复合物的结构：一种具有新型折叠和靶位点识别模式的DNA结合结构域。
Structure of the GCM domain-DNA complex: a DNA-binding domain with a novel fold and mode of target site recognition.
作者信息
Cohen Serge X, Moulin Martine, Hashemolhosseini Said, Kilian Karin, Wegner Michael, Müller Christoph W
机构信息
European Molecular Biology Laboratory, Grenoble Outstation, BP 181, 38042 Grenoble Cedex 9, France.
出版信息
EMBO J. 2003 Apr 15;22(8):1835-45. doi: 10.1093/emboj/cdg182.
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 A 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.
神经胶质细胞缺失（GCM）转录因子在多细胞动物中构成了一个小型的转录调节因子家族。典型的果蝇GCM蛋白指导神经前体细胞分化为神经胶质细胞，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，该区域负责DNA结合，称为GCM结构域。在此，我们展示了来自小鼠GCMa的GCM结构域与其八聚体DNA靶位点结合的晶体结构，分辨率为2.85埃。GCM结构域呈现出一种新颖的折叠结构，由两个结构域通过两个结构锌离子之一连接在一起。我们观察到在DNA识别中β-折叠的新用途，即一个五链β-折叠垂直于DNA轴突入大沟。该结构与靶位点及DNA接触残基的突变分析相结合，为这种新型含锌DNA结合结构域的DNA识别提供了深入见解。
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