Strauss-Soukup J K, Maher L J
Department of Biochemistry and Molecular Biology and Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Biochemistry. 1997 Aug 19;36(33):10026-32. doi: 10.1021/bi970215u.
Transcription activation is thought to require DNA bending to promote the interaction of upstream activators and the basal transcription machinery. Previous experiments have shown that some members of the bZIP family of DNA binding proteins bend DNA, while others do not. We are exploring the possibility that electrostatic effects play a role in these differences. The yeast bZIP transcription factor GCN4 does not induce DNA bending in vitro. Substitution of basic residues for three neutral amino acids of GCN4 confers the ability to bend DNA. This result is consistent with a model of induced DNA bending wherein excess positive charge in proximity to one face of the double helix neutralizes local phosphate diester anions resulting in a laterally asymmetric charge distribution along the DNA. Previous data suggest that such an unbalanced charge distribution results in collapse of the DNA toward the neutralized surface. Interpretations of the present data are discussed. Our result supports the hypothesis that electrostatic interactions can play a key role in DNA bending by bZIP proteins.
转录激活被认为需要DNA弯曲来促进上游激活因子与基础转录机制的相互作用。先前的实验表明,bZIP家族的DNA结合蛋白中的一些成员能使DNA弯曲,而其他成员则不能。我们正在探索静电效应在这些差异中起作用的可能性。酵母bZIP转录因子GCN4在体外不会诱导DNA弯曲。用碱性残基取代GCN4的三个中性氨基酸赋予了其使DNA弯曲的能力。这一结果与诱导DNA弯曲的模型一致,即在双螺旋的一个面附近的过量正电荷中和了局部磷酸二酯阴离子,导致沿DNA的横向不对称电荷分布。先前的数据表明,这种不平衡的电荷分布会导致DNA向中和表面塌陷。本文讨论了对当前数据的解释。我们的结果支持了静电相互作用在bZIP蛋白使DNA弯曲中起关键作用的假设。