Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.

Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.
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DOI:
10.1016/j.tibs.2016.10.003
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发表时间:
2017-01
影响因子:
13.8
通讯作者:
Rodgers, Karla K.
Rodgers, Karla K.
中科院分区:
生物学1区
文献类型:
--
作者:
Rodgers, Karla K.

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获得性免疫系统的发展依赖于V(D)J重组,其通过组分基因片段的重排形成功能性抗原受体基因。由重组激活蛋白RAG1和RAG2组成的V(D)J重组酶将初始DNA切割事件引导至位于每个基因片段侧翼的重组信号序列(RSS)。尽管二十多年前建立了RAG介导的核酸内切活性的酶促步骤,但直到最近才对RAG蛋白的催化活性核心区域的高分辨率结构研究揭示了反应的构象要求。虽然仍有一些悬而未决的问题,但我们对RAG蛋白如何在产生抗原受体的各种库中发挥作用有了更清晰的认识,抗原受体是适应性免疫系统的基础。
Development of the adaptive immune system is dependent on V(D)J recombination, which forms functional antigen receptor genes through rearrangement of component gene segments. The V(D)J recombinase, consisting of recombination-activating proteins RAG1 and RAG2, guides the initial DNA cleavage events to the recombination signal sequence (RSS), which flanks each gene segment. Although the enzymatic steps for RAG-mediated endonucleolytic activity was established over two decades ago, only recently have high resolution structural studies of the catalytically active core regions of the RAG proteins shed light on conformational requirements for the reaction. While outstanding questions remain, we have a clearer picture for how RAG proteins function in generating the diverse repertoires of antigen receptors, the underlying foundation of the adaptive immune system.
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