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10.1016/j.cell.2015.10.055

http://scihub22266oqcxt.onion/10.1016/j.cell.2015.10.055
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C4690471!4690471!26548953
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suck abstract from ncbi


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pmid26548953      Cell 2015 ; 163 (5): 1138-52
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  • Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures #MMPMID26548953
  • Ru H; Chambers MG; Fu TM; Tong AB; Liao M; Wu H
  • Cell 2015[Nov]; 163 (5): 1138-52 PMID26548953show ga
  • Diverse repertoires of antigen-receptor genes that result from combinatorial splicing of coding segments by V(D)J recombination are hallmarks of vertebrate immunity. The (RAG1-RAG2)2 recombinase (RAG) recognizes recombination signal sequences (RSSs) containing a heptamer, a spacer of 12 or 23 base pairs, and a nonamer (12-RSS or 23-RSS) and introduces precise breaks at RSS-coding segment junctions. RAG forms synaptic complexes only with one 12-RSS and one 23-RSS, a dogma known as the 12/23 rule that governs the recombination fidelity. We report cryo-electron microscopy structures of synaptic RAG complexes at up to 3.4 Å resolution, which reveal a closed conformation with base flipping and base-specific recognition of RSSs. Distortion at RSS-coding segment junctions and base flipping in coding segments uncover the two-metal-ion catalytic mechanism. Induced asymmetry involving tilting of the nonamer-binding domain dimer of RAG1 upon binding of HMGB1-bent 12-RSS or 23-RSS underlies the molecular mechanism for the 12/23 rule.
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