Molecular basis for the redox control of nuclear transport of the structural chromatin protein Hmgb1
Molecular basis for the redox control of nuclear transport of the structural chromatin protein Hmgb1
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DOI：
10.1016/j.yexcr.2006.07.020
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发表时间：
2006-11-01
影响因子：
3.7
通讯作者：
Sears, Jonathan E.
中科院分区：
文献类型：
--
作者：
Hoppe, George;Talcott, Katherine E.;Sears, Jonathan E.
氧化应激可以诱导蛋白质和多肽硫醇之间的共价二硫键，这种键通过酶催化是可逆的。这一过程为蛋白质功能的控制提供了一种翻译后机制，也可能保护硫醇基团免受不可逆氧化。高迁移率族蛋白B1(HMGB1)是一种DNA结合的结构染色体蛋白和转录共激活因子，是谷氧还蛋白的底物。HMGB1含有3个半胱氨酸，分别为23、45和106。在温和的氧化条件下，Cys23和Cys45容易形成分子内二硫键，而Cys106保持还原状态。Cys23和Cys45之间的二硫键是谷胱甘肽依赖的谷氧还蛋白还原的靶标。内源性HMGB1和GFP标记的野生型HMGB1共同定位于CHO细胞的细胞核。用丝氨酸替换HMGB1Cys23和/或45不影响突变蛋白的核分布，而Cys106-to-Ser和三重半胱氨酸突变会损害HMGB1的核定位。我们的半胱氨酸靶向突变分析表明，Cys23和45在氧化应激反应中诱导构象变化，而Cys106似乎对HMGB1的核质穿梭至关重要。(C)2006 Elsevier Inc.保留所有权利。
oxidative stress can induce a covalent disulfide bond between protein and peptide thiols that is reversible through enzymatic catalysis. This process provides a post-translational mechanism for control of protein function and may also protect thiol groups from irreversible oxidation. High mobility group protein B1 (Hmgb1), a DNA-binding structural chromosomal protein and transcriptional co-activator was identified as a substrate of glutaredoxin. Hmgb1 contains 3 cysteines, Cys23, 45, and 106. In mild oxidative conditions, Cys23 and Cys45 readily form an intramolecular disulfide bridge, whereas Cys106 remains in the reduced form. The disulfide bond between Cys23 and Cys45 is a target of glutathione-dependent reduction by glutaredoxin. Endogenous Hmgb1 as well as GFP-tagged wild-type Hmgb1 co-localize in the nucleus of CHO cells. While replacement of Hmgb1 Cys23 and/or 45 with serines did not affect the nuclear distribution of the mutant proteins, Cys106-to-Ser and triple cysteine mutations impaired nuclear localization of Hmgb1. Our cysteine targeted mutational analysis suggests that Cys23 and 45 induce conformational changes in response to oxidative stress, whereas Cys106 appears to be critical for the nucleocytoplasmic shuttling of Hmgb1. (c) 2006 Elsevier Inc. All rights reserved.