Institute of Molecular Biology and Genetics, Biomedical Sciences Research Centre, Alexander Fleming, Vari 16672, Greece.
J Biol Chem. 2010 Jan 15;285(3):1692-700. doi: 10.1074/jbc.M109.045989. Epub 2009 Nov 17.
Members of the conserved 14-3-3 protein family spontaneously self-assemble as homo- and heterodimers via conserved sequences in the first four (alphaA-alphaD) of the nine helices that comprise them. Dimeric 14-3-3s bind conserved motifs in diverse protein targets involved in multiple essential cellular processes including signaling, intracellular trafficking, cell cycle regulation, and modulation of enzymatic activities. However, recent mostly in vitro evidence has emerged, suggesting functional and regulatory roles for monomeric 14-3-3s. We capitalized on the simplicity of the 14-3-3 family in Drosophila to investigate in vivo 14-3-3zeta monomer properties and functionality. We report that dimerization is essential for the stability and function of 14-3-3zeta in neurons. Moreover, we reveal the contribution of conserved amino acids in helices A and D to homo- and heterodimerization and their functional consequences on the viability of animals devoid of endogenous 14-3-3zeta. Finally, we present evidence suggesting endogenous homeostatic adjustment of the levels of the second family member in Drosophila, D14-3-3epsilon, to transgenic monomeric and dimerization-competent 14-3-3zeta.
保守的 14-3-3 蛋白家族的成员通过其九个螺旋中的前四个（alphaA-alphaD）中的保守序列自发地组装为同源和异源二聚体。二聚体 14-3-3 与涉及多种基本细胞过程的多种蛋白靶标中的保守基序结合，包括信号转导、细胞内运输、细胞周期调控和酶活性的调节。然而，最近出现了主要来自体外的证据，表明单体 14-3-3 具有功能和调节作用。我们利用果蝇中 14-3-3 家族的简单性来研究体内 14-3-3zeta 单体的性质和功能。我们报告说，二聚化对于神经元中 14-3-3zeta 的稳定性和功能是必不可少的。此外，我们揭示了螺旋 A 和 D 中的保守氨基酸对同源和异源二聚化的贡献及其对缺乏内源性 14-3-3zeta 的动物存活的功能后果。最后，我们提出的证据表明，果蝇中二聚化伴侣 D14-3-3epsilon 的水平存在内源性的稳态调节，以适应转基因组的单体和二聚化能力的 14-3-3zeta。
