Department of Biology, West Virginia University, Life Sciences Building, Morgantown, WV 26506-6057, USA.
Mol Cell Biochem. 2011 Oct;356(1-2):217-25. doi: 10.1007/s11010-011-0996-x. Epub 2011 Jul 26.
CK2 is a Ser/Thr protein kinase that regulates the activity of the Drosophila basic-helix-loop-helix (bHLH) repressor M8 encoded by the Enhancer of split Complex (E(spl)C) during neurogenesis. Specifically, phosphorylation appears to elicit a conformational change in an autoinhibited state of M8 to one that is permissive for repression. We describe biochemical and molecular modeling studies that provide new insights into repression by M8. Our studies implicate the phosphorylation domain in autoinhibition, and indicate that binding of the co-repressor Groucho (Gro) is context-dependent. Molecular modeling indicates that the Orange domain, proposed to be a specificity-determinant, may instead play a structural role, and that a conformational rearrangement of this domain may be necessary for repression. This model also provides a structural mechanism for the behavior of mutant alleles of the m8 gene. The insights gained from these studies should be applicable to the conserved metazoan bHLH repressors of the Hairy and Enhancer of Split (HES) family that are related to Drosophila M8.
CK2 是一种丝氨酸/苏氨酸蛋白激酶，可调节果蝇基本螺旋-环-螺旋（bHLH）转录阻遏物 M8 的活性，M8 由 Spl 增强子复合物（E(spl)C）编码，在神经发生过程中起作用。具体来说，磷酸化似乎会引起 M8 的自动抑制状态发生构象变化，使其变为允许抑制的状态。我们描述了生化和分子建模研究，这些研究为 M8 的抑制作用提供了新的见解。我们的研究表明，磷酸化结构域在自动抑制中起作用，并表明共抑制因子 Groucho（Gro）的结合具有上下文依赖性。分子建模表明，橙色结构域，拟议为特异性决定因素，可能发挥结构作用，并且该结构域的构象重排可能是抑制所必需的。该模型还为 m8 基因突变体的行为提供了一个结构机制。这些研究获得的见解应该适用于与果蝇 M8 相关的保守后生动物 bHLH 转录阻遏物的 Hairy 和 Enhancer of Split（HES）家族。
