The Dimerization State of the Mammalian High Mobility Group Protein AT-Hook 2 (HMGA2).

The Dimerization State of the Mammalian High Mobility Group Protein AT-Hook 2 (HMGA2).
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哺乳动物高迁移率蛋白AT-HOC 2(HMGA2)的二聚化状态。

DOI:
10.1371/journal.pone.0130478
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Leng F
Leng F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Frost L;Baez MA;Harrilal C;Garabedian A;Fernandez-Lima F;Leng F

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哺乳动物高迁移率族蛋白AT-钩2(HMGA 2)是一种参与细胞转化和肿瘤发生的染色体结构转录因子。它由三个带正电荷的“AT-钩”和一个带负电荷的C-末端组成。序列分析、圆二色谱实验和凝胶过滤研究表明,HMGA 2在天然状态下不具有确定的二级或三级结构。令人惊讶的是,使用1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC)化学交联、分析超离心、荧光共振能量转移(FRET)和质谱的组合方法,我们发现HMGA 2能够在水性缓冲溶液中自缔合成同源二聚体。我们的研究结果表明,带正电荷的“AT-钩”和带负电荷的C-末端之间的静电相互作用大大有助于同源二聚体的形成。
The mammalian high mobility group protein AT-hook 2 (HMGA2) is a chromosomal architectural transcription factor involved in cell transformation and oncogenesis. It consists of three positively charged “AT-hooks” and a negatively charged C-terminus. Sequence analyses, circular dichroism experiments, and gel-filtration studies showed that HMGA2, in the native state, does not have a defined secondary or tertiary structure. Surprisingly, using combined approaches of 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemical cross-linking, analytical ultracentrifugation, fluorescence resonance energy transfer (FRET), and mass spectrometry, we discovered that HMGA2 is capable of self-associating into homodimers in aqueous buffer solution. Our results showed that electrostatic interactions between the positively charged “AT-hooks” and the negatively charged C-terminus greatly contribute to the homodimer formation.
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