Brandt-Rauf P W, Pincus M R, Chen J M, Lee G
Division of Environmental Sciences, Columbia-Presbyterian Medical Center, New York, New York 10032.
J Protein Chem. 1989 Oct;8(5):679-88. doi: 10.1007/BF01025608.
It has been recently proposed that certain DNA binding proteins (including C/EBP, GCN4 and the myc, jun, and fos oncogene proteins) share a common structural motif based on helix-promoting regions containing heptad repeat sequences of leucines. It has been suggested that this structure is critical to the biological activity of these proteins, since it facilitates the formation of functional dimers held together by interdigitating leucine side-chains along the hydrophobic interfaces between long alpha-helical regions of the polypeptide chains in a configuration termed the "leucine zipper." In this paper, conformational energy analysis is used to deterrmine the preferred three-dimensional structures of the leucine repeat regions of these proteins. The results indicate that, in all cases, the global minimum energy conformation for these regions is an amphipathic alpha-helix with the leucine side-chains arrayed on one side in such a way to favor "leucine zipper" dimerization. Furthermore, amino acid substitutions in these regions (such as Pro for Leu), that are known to inhibit dimer formation and prevent DNA binding, are found to produce significant conformational changes that disrupt the amphipathic helical structure. Thus, these results provide support for the proposed "leucine zipper" configuration as a critical structural feature of this class of DNA binding proteins.
最近有人提出，某些DNA结合蛋白（包括C/EBP、GCN4以及myc、jun和fos癌基因蛋白）基于包含亮氨酸七肽重复序列的螺旋促进区域具有共同的结构基序。有人认为这种结构对这些蛋白质的生物活性至关重要，因为它有助于形成功能性二聚体，这些二聚体通过沿着多肽链长α-螺旋区域之间的疏水界面相互交错的亮氨酸侧链结合在一起，形成一种称为“亮氨酸拉链”的构象。在本文中，构象能量分析被用于确定这些蛋白质亮氨酸重复区域的优选三维结构。结果表明，在所有情况下，这些区域的全局最低能量构象是一种两亲性α-螺旋，亮氨酸侧链排列在一侧，有利于“亮氨酸拉链”二聚化。此外，已知这些区域中的氨基酸取代（如用脯氨酸取代亮氨酸）会抑制二聚体形成并阻止DNA结合，结果发现会产生显著的构象变化，破坏两亲性螺旋结构。因此，这些结果为所提出的“亮氨酸拉链”构象作为这类DNA结合蛋白的关键结构特征提供了支持。
