A hallmark of vertebrate immunity is the diverse repertoire of antigen-receptor genes that results from combinatorial splicing of gene coding segments by V(D)J recombination. The (RAG1-RAG2)2 endonuclease complex (RAG) specifically recognizes and cleaves a pair of recombination signal sequences (RSSs), 12-RSS and 23-RSS, via the catalytic steps of nicking and hairpin formation. Both RSSs immediately flank the coding end segments and are composed of a conserved heptamer, a conserved nonamer, and a non-conserved spacer of either 12 base pairs (bp) or 23 bp in between. A single RAG complex only synapses a 12-RSS and a 23-RSS, which was denoted the 12/23 rule, a dogma that ensures recombination between V, D and J segments, but not within the same type of segments. This review recapitulates current structural studies to highlight the conformational transformations in both the RAG complex and the RSS during the consecutive steps of catalysis. The emerging structural mechanism emphasizes distortion of intact RSS and nicked RSS exerted by a piston-like motion in RAG1 and by dimer closure, respectively. Bipartite recognition of heptamer and nonamer, flexibly linked nonamer-binding domain dimer relatively to the heptamer recognition region dimer, and RSS plasticity and bending by HMGB1 together contribute to the molecular basis of the 12/23 rule in the RAG molecular machine.

中文翻译：

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V（D）J重组中RAG介导的DNA切割的结构体操。

脊椎动物免疫的标志是抗原受体基因的多样性，这是通过V（D）J重组对基因编码片段进行组合剪接而产生的。（RAG1-RAG2）2核酸内切酶复合物（RAG）通过切口和发夹形成的催化步骤特异性识别并裂解一对重组信号序列（RSSs），12-RSS和23-RSS。两个RSS都紧接在编码末端片段的侧面，由保守的七聚体，保守的九聚体和介于两者之间的12个碱基对（bp）或23 bp的非保守间隔区组成。一个单一的RAG复合体仅突触一个12-RSS和一个23-RSS，这被称为12/23规则，这是一个确保V，D和J段之间重组的教条，但不在同一类型的段内。这篇综述概述了当前的结构研究，以突出在连续催化步骤中RAG络合物和RSS的构象转化。新兴的结构机制强调了完整的RSS的变形以及RAG1中类似活塞的运动和二聚体闭合所造成的切刻RSS。七聚体和九聚体的二分识别，相对于七聚体识别区域二聚体的柔性连接的九聚体结合域二聚体，以及HMGB1的RSS可塑性和弯曲共同构成了RAG分子机器中12/23规则的分子基础。分别。七聚体和九聚体的二分识别，相对于七聚体识别区域二聚体的柔性连接的九聚体结合域二聚体，以及HMGB1的RSS可塑性和弯曲共同构成了RAG分子机器中12/23规则的分子基础。分别。七聚体和九聚体的二分识别，相对于七聚体识别区域二聚体的柔性连接的九聚体结合域二聚体，以及HMGB1的RSS可塑性和弯曲共同构成了RAG分子机器中12/23规则的分子基础。