Three-dimensional clustering of human RAG2 gene mutations in severe combined immune deficiency
Three-dimensional clustering of human RAG2 gene mutations in severe combined immune deficiency
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DOI：
10.1074/jbc.275.17.12672
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发表时间：
2000-04-28
影响因子：
4.8
通讯作者：
de Villartay, JP
中科院分区：
文献类型：
--
作者：
Corneo, B;Moshous, D;de Villartay, JP
V(D)J重组导致可变、多样性和连接片段的体细胞重排，是T细胞受体和igg编码基因多样性的机制。RAG1和RAG2基因的产物是通过产生DNA双链断裂引发V(D)J重组的淋巴特异性因子。小鼠RAGI或RAG2基因失活导致V(D)J重排过程流产，T细胞和B细胞成熟早期阻滞，最终导致严重的联合免疫缺陷（SCID）。人类SCID的另一个特征是缺乏成熟的T淋巴细胞和B淋巴细胞，并与RAG1-或rag2编码基因的突变有关。基于预测的RAGS的β -螺旋桨三维结构模型，我们发现迄今为止在T-B-SCID患者中描述的7个突变中有6个聚集在螺旋桨的一侧，在暴露于溶剂的区域。这一发现加强了该预测模型的生物学意义，并表明RAG1与β -螺旋桨形成的支架一侧的rag相互作用。
The V(D)J recombination, which leads to the somatic rearrangement of variable, diversity, and joining segments, is the mechanism accountable for the diversity of T cell receptor- and Ig-encoding genes. The products of the RAG1 and RAG2 genes are the lymphoid-specific factors responsible for the initiation of the V(D)J recombination through the generation of a DNA double strand break. RAGI or RAG2 gene inactivation in the mouse leads to abortion of the V(D)J rearrangement process, early block in both T and B cell maturation, and, ultimately, to severe combined immune deficiency (SCID). A human SCID condition is also characterized by an absence of mature T and B lymphocytes and is associated with mutations in either RAG1- or RAG2-encoding genes. Based on the predicted beta-propeller three-dimensional structure model for RAGS, we found that six out of the seven mutations described to date in T-B-SCID patients are clustered on one side of the propeller, in regions exposed to solvent. This finding reinforces the biological significance of this predicted model and suggests that RAG1 interacts with RAGS on one of the side of the scaffold formed by the beta-propeller.