鼠源FiliaN端蛋白在GSH条件中的一种全新三维结构

A Novel Structure of Mus musculus Filia N-terminal Protein Grown in Solution With GSH

母性效应因子复合体SCMC(subcorticalmaternalcomplex)中的Filia蛋白,其N端具有Ⅰ型KH结构域的特征,通过结合RNA参与卵子发生及胚胎发育过程中的RNA转录调控.此外,Filia蛋白对染色体整倍体化的维持起重要作用.缺乏Filia的雌鼠体内早期胚胎发育进程延迟,致使雌鼠生殖力降低,但不会不育.在卵母细胞成熟过程中,还原型谷胱甘肽(glutathione,GSH)浓度发生变化以维持胞内的氧化还原环境.本文成功解析了在含有GSH的条件中生长的Filia(N1-124)蛋白晶体结构.与在不含GSH的条件中生长的Filia(N1-124)蛋白晶体相比,在含有GSH的条件中,Filia(N1-124)蛋白晶体的一个不对称单位中含有5对二聚体,Filia(N1-124)单体分子在α3螺旋区与邻近分子发生了结构域交换.Filia(N1-124)晶体内凭借链间的离子键、氢键和疏水相互作用,形成了独特的十聚体组装方式.本文为进一步研究在不同生理条件下Filia的结构与功能的关系提供了结构依据.

Filia is one of the components of maternal Subcortical Maternal Complex（SCMC）. The N-terminal of Filia is similar to KH domain of type I family, which play roles in transcription regulation in oogenesis and embryo development by binding RNA. Additionally, maternal Filia plays essential role in maintaining euploidy. The absence of maternal Filia appears to delay embryonic progression, which can decrease the number of offspring rather than sterile. During oocyte maturation stage, the concentration of GSH varied to keep balance of oxidation-reduction. Our crystallographic studies successfully reveal the structure of Filia N-terminal protein grown in solution with GSH. In contrast with the structure of Filia N-terminal protein grown in condition free of GSH, protein grown in GSH have five pairs of dimer in an asymmetry unit. Domain swapping occurs in the α3-helix of Filia （N1-124） molecules. A special decamer structure is formed by ionic interaction, H-bond and hydrophobic interaction. The Filia N-terminal structure provides a structural foundation for further researches on the structure and function of Filia in diversity physiological environment.