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

Article

关键词: DNA HAIRPIN FORMATION;    AMINO-ACID-RESIDUES;    SINGLE ACTIVE-SITE;    MUTATIONAL ANALYSIS;    BINDING DOMAIN;    RAG2 PROTEINS;    COMPLEX;    TRANSPOSITION;    CLEAVAGE;    RAG1/2;   

DOI  :  10.1038/nature14174

来源: SCIE

【 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.

【 授权许可】

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