Gibson T J, Postma J P, Brown R S, Argos P
European Molecular Biology Laboratory, Heidelberg, FRG.
Protein Eng. 1988 Sep;2(3):209-18. doi: 10.1093/protein/2.3.209.
Many eukaryotic transcriptional activator proteins, including the Xenopus 5S RNA gene activator protein TFIIIA and the HeLa cell protein Sp1, have an approximately 30 amino acid repeating motif which binds to short, specific DNA sequences. Over 150 of these sequences are now known. Based on the observed distribution of amino acid residues, a series of constraints and predictions can be proposed for the structure of the motif. A compatible three-dimensional structural model has been developed by a combination of interactive model building and refinement by molecular dynamics. The model structure consists of a two-stranded beta-hairpin stabilizing a C-terminal alpha-helix by both zinc ligands and hydrophobic interactions. Four of the residue positions on the helix N-terminus and exposed face are predicted to provide base specific ligands. Further implications of the model for DNA binding are discussed.
许多真核转录激活蛋白，包括非洲爪蟾5S RNA基因激活蛋白TFIIIA和海拉细胞蛋白Sp1，都有一个约30个氨基酸的重复基序，该基序可与短的特定DNA序列结合。目前已知超过150种此类序列。基于观察到的氨基酸残基分布，可以对该基序的结构提出一系列限制和预测。通过交互式模型构建和分子动力学优化相结合的方法，已开发出一个兼容的三维结构模型。该模型结构由一个双链β-发夹结构组成，通过锌配体和疏水相互作用稳定C端α-螺旋。预计螺旋N端和暴露面上的四个残基位置可提供碱基特异性配体。文中还讨论了该模型对DNA结合的进一步影响。
