Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding
Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding
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DOI：
10.1101/gad.13.10.1263
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发表时间：
1999-05-15
影响因子：
10.5
通讯作者：
Pabo, CO
中科院分区：
文献类型：
--
作者：
Xu, HE;Rould, MA;Pabo, CO
Pax6是一种转录因子，含有两段配对的DNA结合域，在眼、鼻、胰腺和中枢神经系统的发育中起着关键作用。人Pax6配对结构域的2.5Angstrom结构及其最佳的26bp位点显示了来自氨基末端亚域、连接区和羧基末端亚域的广泛的DNA接触。Pax6的结构不仅证实了果蝇PRD Pax蛋白共晶体中氨基末端亚域的对接排列，而且揭示了这一区域的一些有趣的差异，有助于解释配对结构域-DNA识别的序列特异性。此外，这种结构还提供了有关成对的连接区和羧基末端亚域如何接触DNA的第一个详细信息。延伸的连接体在8个碱基点的区域上进行小槽接触，而羧基末端螺旋-回转螺旋单元在主槽中进行底座接触。Pax6的羧基末端亚域的结构和对接排列与氨基末端亚域的结构和对接排列非常相似，并且这两个螺旋-转角-螺旋单元的多肽骨架之间有大约两个对称轴。我们的Pax6配对结构域-DNA复合体的结构为理解配对结构域-DNA相互作用、分析映射在配对结构域的连接子和羧基末端区域的突变以及建模Pax家族蛋白质的蛋白质-蛋白质相互作用提供了一个框架。
Pax6, a transcription factor containing the bipartite paired DNA-binding domain, has critical roles in development of the eye, nose, pancreas, and central nervous system. The 2.5 Angstrom structure of the human Pax6 paired domain with its optimal 26-bp site reveals extensive DNA contacts from the amino-terminal subdomain, the linker region, and the carboxy-terminal subdomain. The Pax6 structure not only confirms the docking arrangement of the amino-terminal subdomain as seen in cocrystals of the Drosophila Prd Pax protein, but also reveals some interesting differences in this region and helps explain the sequence specificity of paired domain-DNA recognition. In addition, this structure gives the first detailed information about how the paired linker region and carboxy-terminal subdomain contact DNA. The extended linker makes minor groove contacts over an 8-bp region, and the carboxy-terminal helix-turn-helix unit makes base contacts in the major groove. The structure and docking arrangement of the carboxy-terminal subdomain of Pax6 is remarkably similar to that of the amino-terminal subdomain, and there is an approximate twofold symmetry axis relating the polypeptide backbones of these two helix-turn-helix units. Our structure of the Pax6 paired domain-DNA complex provides a framework for understanding paired domain-DNA interactions, for analyzing mutations that map in the linker and carboxy-terminal regions of the paired domain, and for modeling protein-protein interactions of the Pax family proteins.