Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.
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, comprising 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 were 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 of how RAG proteins function in generating the diverse repertoires of antigen receptors, the underlying foundation of the adaptive immune system.
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. Electronic address: karla-rodgers@ouhsc.edu.
Karla K
KK
Rodgers
D000818:Animals; D053903:DNA Breaks, Double-Stranded; D053837:DNA Cleavage; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D045567:VDJ Recombinases / Q000737:chemistry* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D045567:VDJ Recombinases
RAG1; RAG2; V(D)J recombination; lymphocyte development