title: Crystal structure of the V(D)J recombinase RAG1-RAG2.
abstract: 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 3.2 Å 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.
authors.affiliation: Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Min-Sung
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Mikalai
authors.initials: M
authors.lastname: Lapkouski
authors.affiliation: Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Gellert
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D016511:Severe Combined Immunodeficiency / Q000235:genetics; D019895:Transposases / Q000737:chemistry; D045567:VDJ Recombinases / Q000737:chemistry* / Q000378:metabolism; D053632:X-Linked Combined Immunodeficiency Diseases / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA; D019895:Transposases; D045567:VDJ Recombinases