Crystal structure of the V(D) J recombinase RAG1-RAG2

摘要

V(D)J recombination in the vertebrate immune system generates a highly diverse population of immunoglobulins and T-cell receptors by combinatorial joining of segments of coding DNA. The RAG1-RAG2 protein complex initiates this site-specific recombination by cutting DNA at specific sites flanking the coding segments. Here we report the crystal structure of the mouse RAG1-RAG2 complex at 3.2A resolution. The 230-kilodalton RAG1-RAG2 heterotetramer is *Y-shaped', with the amino-terminal domains of the two RAG1 chains forming an intertwined stalk. Each RAG1-RAG2 heterodimer composes one arm of the' Y', with the active site in the middle and RAG2 at its tip. The RAG1-RAG2 structure rationalizes more than 60 mutations identified in immunodeficient patients, as well as a large body of genetic and biochemical data. The architectural similarity between RAG1 and the hairpin-forming transposases Hermes and Tn5 suggests the evolutionary conservation of these DNA rearrangements.%脊椎动物免疫系统利用V(D)J重组来从有限的编码片段库中产生编码免疫球蛋白和T-细胞受体的大量不同基因。这一重组过程由分裂复合物RAG1-RAG2启动。现在,Wei Yang及同事以3.2A的分辨率获得了RAG1-RAG2重组酶异四聚体的晶体结构。该复合物形成一个Y-形结构,其中每个臂含有一个RAG1-RAG2异二聚体。整体结构与能形成"发卡"的转座酶的结构相似,从而证明了其作为一种专门形式的转座活性的演化历史。该结构让我们认识了V(D)J重组的机制,也为很多致病突变提供了基础。