Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany.
Institute of Immunology, Medical Faculty Carl Gustav Carus Dresden, Technical University Dresden, 01307 Dresden, Germany.
Int J Mol Sci. 2021 Mar 25;22(7):3377. doi: 10.3390/ijms22073377.
According to the literature, the autoantigen La is involved in Cap-independent translation. It was proposed that one prerequisite for this function is the formation of a protein dimer. However, structural analyses argue against La protein dimers. Noteworthy to mention, these structural analyses were performed under reducing conditions. Here we describe that La protein can undergo redox-dependent structural changes. The oxidized form of La protein can form dimers, oligomers and even polymers stabilized by disulfide bridges. The primary sequence of La protein contains three cysteine residues. Only after mutation of all three cysteine residues to alanine La protein becomes insensitive to oxidation, indicating that all three cysteines are involved in redox-dependent structural changes. Biophysical analyses of the secondary structure of La protein support the redox-dependent conformational changes. Moreover, we identified monoclonal anti-La antibodies (anti-La mAbs) that react with either the reduced or oxidized form of La protein. Differential reactivities to the reduced and oxidized form of La protein were also found in anti-La sera of autoimmune patients.
根据文献，自身抗原 La 参与了非依赖性翻译。有人提出，该功能的一个前提条件是形成蛋白质二聚体。然而，结构分析却不支持 La 蛋白二聚体。值得一提的是，这些结构分析是在还原条件下进行的。在这里，我们描述了 La 蛋白可以发生氧化还原依赖性的结构变化。La 蛋白的氧化形式可以形成二聚体、寡聚体甚至聚合物，这些聚合物由二硫键稳定。La 蛋白的一级序列包含三个半胱氨酸残基。只有当所有三个半胱氨酸残基突变为丙氨酸时，La 蛋白才对氧化不敏感，这表明所有三个半胱氨酸都参与了氧化还原依赖性的结构变化。La 蛋白二级结构的生物物理分析支持氧化还原依赖性构象变化。此外，我们鉴定了与 La 蛋白的还原或氧化形式反应的单克隆抗-La 抗体（抗-La mAbs）。自身免疫患者的抗-La 血清中也发现了对 La 蛋白还原和氧化形式的不同反应性。
