Intramolecular Regulation of MyoD Activation Domain Conformation and Function

Jing Huang; Hal Weintraub; Larry Kedes

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Intramolecular Regulation of MyoD Activation Domain Conformation and Function

机译：MyoD激活域构象和功能的分子内调控。

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The MyoD family of basic helix-loop-helix (bHLH) proteins is required for myogenic determination and differentiation. The basic region carries the myogenic code and DNA binding specificity, while the N terminus contains a potent transcriptional activation domain. Myogenic activation is abolished when the basic region, bound to a myogenic E box, carries a mutation of Ala-114. It has been proposed that DNA binding of the MyoD basic region leads to recruitment of a recognition factor that unmasks the activation domain. Here we demonstrate that an A114N mutant exhibits an altered conformation in the basic region and that this local conformational difference can lead to a more global change affecting the conformation of the activation domain. This suggests that the deleterious effects of this class of mutations may result directly from defective conformation. Thus, the activation domain is unmasked only upon DNA binding by the correct basic region. Such a coupled conformational relationship may have evolved to restrict myogenic specificity to a small number of bHLH proteins among many with diverse functions yet with DNA binding specificities known to be similar.

机译：基本的螺旋-环-螺旋（bHLH）蛋白的MyoD家族是成肌测定和分化所必需的。基本区域带有肌原性密码和DNA结合特异性，而N端则含有有效的转录激活结构域。当与成肌E盒结合的基本区域携带Ala-114突变时，成肌激活被取消。已经提出，MyoD基本区域的DNA结合导致募集不掩盖激活结构域的识别因子。在这里，我们证明了一个A114N突变体在基本区域表现出改变的构象，并且这种局部构象差异可能导致影响激活域构象的整体变化。这表明这类突变的有害作用可能直接由有缺陷的构象引起。因此，仅当DNA被正确的碱性区域结合时，激活结构域才被掩盖。这种偶联的构象关系可能已经进化为将肌原性特异性限制在少数具有多种功能但DNA结合特异性相似的bHLH蛋白中。

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《Molecular and Cellular Biology》 |1998年第9期|共7页
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Jing Huang; Hal Weintraub; Larry Kedes;
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中图分类细胞生物学;
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1. Conformational Dynamics, Intramolecular Domain Conformation Signaling, and Activation of Apo-FimD Revealed by Single-Molecule Fluorescence Resonance Energy Transfer Studies [J] . Liu Yanqing, Sun Chuanqi, Han Long, Biochemistry . 2019,第14期

机译：单分子荧光共振能量转移研究表明，单分子荧光共振能量转移研究揭示的构象动态，分子内域构象信号和APO-FIMD的激活
2. The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and myoD. [J] . Bailey P, Sartorelli V, Hamamori Y, Nucleic Acids Research . 1998,第23期

机译：孤儿核受体COUP-TF II通过转录后调节MyoD功能来抑制肌发生：COUP-TF II直接与p300和myoD相互作用。
3. The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and MyoD [J] . George E. O. Muscat, Peter Bailey, Vittorio Sartorelli, Nucleic acids research . 1998,第23期

机译：孤儿核受体COUP-TF II通过转录后调节MyoD功能抑制肌发生：COUP-TF II直接与p300和MyoD相互作用
4. Conformational activation of 2 integrins, their I domains, and regulation by small molecule antagonists [C] . Springer, T.A., Shimaoka, . 2002

机译：2个整联蛋白的构象激活，它们的I结构域和小分子拮抗剂的调控
5. Gene expression in wild-type and MyoD-null satellite cells: Regulation of activation, proliferation, and myogenesis. [D] . Cornelison, Dawn D. W. 1998

机译：野生型和MyoD-null卫星细胞中的基因表达：激活，增殖和肌生成的调节。
6. Intramolecular Regulation of MyoD Activation Domain Conformation and Function [O] . Jing Huang, Hal Weintraub, Larry Kedes 1998

机译：MyoD激活域构象和功能的分子内调控。
7. Intramolecular regulation of MyoD activation domain conformation and function [O] . Jing Huang, Hal Weintraub, Larry Kedes 1998

机译：myoD激活域构象和功能的分子内调节

Intramolecular Regulation of MyoD Activation Domain Conformation and Function

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