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首页> 外文期刊>Molecular and Cellular Biology >Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them.
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Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them.

机译：脆弱的X综合征蛋白FMR1和FXR蛋白中的特定序列介导它们与60S核糖体亚基的结合以及它们之间的相互作用。

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Fragile X syndrome, the most common form of hereditary mental retardation, usually results from lack of expression of the FMR1 gene. The FMR1 protein is a cytoplasmic RNA-binding protein. The RNA-binding activity of FMR1 is an essential feature of FMR1, as fragile X syndrome can also result from the expression of mutant FMR1 protein that is impaired in RNA binding. Recently, we described two novel cytoplasmic proteins, FXR1 and FXR2, which are both very similar in amino acid sequence to FMR1 and which also interact strongly with FMR1 and with each other. To understand the function of FMR1 and the FXR proteins, we carried out cell fractionation and sedimentation experiments with monoclonal antibodies to these proteins to characterize the complexes they form. Here, we report that the FMR1 and FXR proteins are associated with ribosomes, predominantly with 60S large ribosomal subunits. The FXR proteins are associated with 60S ribosomal subunits even in cells that lack FMR1 and that are derived from a fragile X syndrome patient, indicating that FMR1 is not required for this association. We delineated the regions of FMR1 that mediate its binding to 60S ribosomal subunits and the interactions among the FMR1-FXR family members. Both regions contain sequences predicted to have a high propensity to form coiled coil interactions, and the sequences are highly evolutionarily conserved in this protein family. The association of the FMR1, FXR1, and FXR2 proteins with ribosomes suggests they have functions in translation or mRNA stability.
机译：脆性X综合征是遗传性智力低下的最常见形式，通常是由于缺乏FMR1基因的表达所致。 FMR1蛋白是一种细胞质RNA结合蛋白。 FMR1的RNA结合活性是FMR1的基本特征，因为脆弱的X综合征也可能是由于RNA结合受损的突变FMR1蛋白的表达所致。最近，我们描述了两个新颖的胞质蛋白FXR1和FXR2，它们在氨基酸序列上与FMR1非常相似，并且也与FMR1以及彼此强烈相互作用。为了了解FMR1和FXR蛋白的功能，我们进行了针对这些蛋白的单克隆抗体的细胞分离和沉降实验，以表征它们形成的复合物。在这里，我们报告FMR1和FXR蛋白与核糖体有关，主要与60S大核糖体亚基有关。即使在缺乏FMR1且来自易碎X综合征患者的细胞中，FXR蛋白也与60S核糖体亚基相关，这表明该关联不需要FMR1。我们描述了FMR1介导其与60S核糖体亚基结合的区域，以及FMR1-FXR家族成员之间的相互作用。这两个区域均包含被预测具有形成卷曲螺旋相互作用的高序列的序列，并且该序列在该蛋白质家族中高度进化保守。 FMR1，FXR1和FXR2蛋白与核糖体的关联表明它们具有翻译或mRNA稳定性的功能。

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