Callebaut I, Mornon J P
Systèmes moléculaires et Biologie structurale, LMCP, CNRS UMR C7590, Paris, France.
Cell Mol Life Sci. 1998 Aug;54(8):880-91. doi: 10.1007/s000180050216.
The RAG1 and RAG2 proteins play a crucial role in V(D)J recombination by cooperating to make specific double-stranded DNA breaks at a pair of recombination signal sequences (RSSs). However, the exact function they perform has heretofore remained elusive. Using a combination of sensitive methods of sequence analysis, we show here that the active core region of the RAG2 protein, confined to the first three quarters of its sequence, is in fact composed of a six-fold repeat of a 50-residue motif which is related to the kelch/mipp motif. This motif, which forms a four-stranded twisted antiparallel beta sheet, is arranged in a circular formation like blades of a propeller or turbine. Given the known properties of the beta-propeller fold in mediating protein-protein interactions, it is proposed that this six-laded propeller structure of the RAG2 active core would play a crucial role in the tight complex formed by the RAG1 and RAG2 proteins and RSSs. Moreover, the presence of a plant homeodomain finger-like motif in the last quarter of the RAG2 sequence suggests a potential interaction of this domain with chromatin components.
RAG1和RAG2蛋白通过协同作用在一对重组信号序列（RSSs）处产生特定的双链DNA断裂，在V(D)J重组中发挥关键作用。然而，它们执行的确切功能迄今仍不清楚。通过结合敏感的序列分析方法，我们在此表明，RAG2蛋白的活性核心区域局限于其序列的前三分之四，实际上由一个50个残基基序的六重重复组成，该基序与kelch/mipp基序相关。这个基序形成一个四链扭曲的反平行β折叠片，像螺旋桨或涡轮机的叶片一样呈圆形排列。鉴于β-螺旋桨折叠在介导蛋白质-蛋白质相互作用方面的已知特性，有人提出RAG2活性核心的这种六叶螺旋桨结构在由RAG1和RAG2蛋白与RSSs形成的紧密复合物中起关键作用。此外，RAG2序列最后四分之一中存在植物同源结构域指状基序，表明该结构域与染色质成分可能存在相互作用。
