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首页> 外文期刊>Biochemistry >STRUCTURAL STUDIES OF MUTANT GLUCOCORTICOID RECEPTOR TRANSACTIVATION DOMAINS ESTABLISH A LINK BETWEEN TRANSACTIVATION ACTIVITY IN VIVO AND ALPHA-HELIX-FORMING POTENTIAL IN VITRO
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STRUCTURAL STUDIES OF MUTANT GLUCOCORTICOID RECEPTOR TRANSACTIVATION DOMAINS ESTABLISH A LINK BETWEEN TRANSACTIVATION ACTIVITY IN VIVO AND ALPHA-HELIX-FORMING POTENTIAL IN VITRO

机译:突变型糖皮质激素受体转化域的结构研究建立了体内的转化活性与体外形成α-螺旋的潜力之间的联系

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摘要

We have previously shown, using circular dichroism spectroscopy, that the tau l 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 l core peptide is a 58-amino acid peptide, constituting the core of the transactivation activity of the tau l 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 l 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.
机译:先前我们已经使用圆二色性光谱表明,τ1核心肽在体外具有形成α-螺旋的潜能[Dahlman-Wright等人。 (1995)美国国家科学院院刊。 Natl。科学院美国92; 1699-1703]。 tau1核心肽是58个氨基酸的肽,构成人糖皮质激素受体的tau1主要反式激活结构域的反式激活活性的核心[Dahlman-Wright等人,J.Biol.Chem。,1987。 (1994)美国国家科学院院刊。 Natl。学院科学美国,91,1619-1623年]。使用NMR光谱对该肽进行进一步的结构研究,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的降低或稳定性与拟议的α-螺旋区中脯氨酸取代的tau l核心肽的体内反式激活潜力无关。而是,相应的纯化肽在体外降低的α-螺旋倾向表明,α-螺旋参与糖皮质激素受体介导的基因活性变化的分子机制。

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