Biophysical characterization reveals structural disorder in the developmental transcriptional regulator LBH.

Biophysical characterization reveals structural disorder in the developmental transcriptional regulator LBH.
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DOI:
10.1016/j.bbrc.2009.12.032
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发表时间:
2010-01-01
影响因子:
3.1
通讯作者:
Briegel, Karoline J.
Briegel, Karoline J.
中科院分区:
生物学4区
文献类型:
--
作者:
Al-Ali, Hassan;Rieger, Megan E.;Seldeen, Kenneth L.;Harris, Thomas K.;Farooq, Amjad;Briegel, Karoline J.

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肢芽和心脏(LBH)是脊椎动物中的关键转录调节因子,在胚胎发育和人类疾病中发挥着关键作用。在此,我们使用多种生物物理技术,报告了 LBH 与其生物学功能相关的第一个结构特征。我们的数据表明,LBH 结构无序,没有可辨别的二级或三级结构,并且在溶液中具有棒状特性。与这些观察结果一致,我们还证明 LBH 具有构象灵活性,因此可能能够在特定的生理环境下适应不同的构象。我们认为 LBH 是本质无序蛋白 (IDP) 家族的一员,构象可塑性可能在调节 LBH 依赖性转录过程中发挥重要作用。
Limb-bud and heart (LBH) is a key transcriptional regulator in vertebrates with pivotal roles in embryonic development and human disease. Herein, using a diverse array of biophysical techniques, we report the first structural characterization of LBH pertinent to its biological function. Our data reveal that LBH is structurally disordered with no discernable secondary or tertiary structure and exudes rod-like properties in solution. Consistent with these observations, we also demonstrate that LBH is conformationally flexible and thus may be capable of adapting distinct conformations under specific physiological contexts. We propose that LBH is a member of the intrinsically disordered protein (IDP) family, and that conformational plasticity may play a significant role in modulating LBH-dependent transcriptional processes.
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