Dahlman-Wright K, McEwan I J
Department of Biosciences, NOVUM, Karolinska Institutet, Huddinge, Sweden.
Biochemistry. 1996 Jan 30;35(4):1323-7. doi: 10.1021/bi952409k.
We have previously shown, using circular dichroism spectroscopy, that the tau 1 core peptide has alpha-helix-forming potential in vitro [Dahlman-Wright et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 1699-1703]. The tau 1 core peptide is a 58-amino acid peptide, constituting the core of the transactivation activity of the tau 1 major transactivation domain of the human glucocorticoid receptor [Dahlman-Wright et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 1619-1623]. Further structural studies of the peptide, using NMR spectroscopy, identified three segments with alpha-helical character. In this report we show that reduced protein expression or stability is not responsible for the reduced in vivo transactivation potential of tau 1 core peptides with proline substitutions in proposed alpha-helical regions. Rather, the reduced alpha-helix propensity of the corresponding purified peptides in vitro suggests that alpha-helices are involved in the molecular mechanism of glucocorticoid receptor mediated changes in gene activity.
我们之前利用圆二色光谱表明，tau 1核心肽在体外具有形成α-螺旋的潜力[达尔曼-赖特等人（1995年）《美国国家科学院院刊》92卷，第1699 - 1703页]。tau 1核心肽是一种由58个氨基酸组成的肽，构成了人类糖皮质激素受体tau 1主要反式激活结构域反式激活活性的核心[达尔曼-赖特等人（(1994年）《美国国家科学院院刊》91卷，第1619 - 1623页]。使用核磁共振光谱对该肽进行的进一步结构研究确定了三个具有α-螺旋特征的片段。在本报告中，我们表明，蛋白质表达或稳定性降低并非tau 1核心肽在体内反式激活潜力降低的原因，这些肽在拟α-螺旋区域存在脯氨酸取代。相反，相应的纯化肽在体外α-螺旋倾向降低表明，α-螺旋参与了糖皮质激素受体介导的基因活性变化的分子机制。
