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PDBsum entry 3jbw
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Recombination/DNA
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PDB id
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3jbw
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References listed in PDB file
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Key reference
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Title
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Molecular mechanism of V(d)j recombination from synaptic rag1-Rag2 complex structures.
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Authors
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H.Ru,
M.G.Chambers,
T.M.Fu,
A.B.Tong,
M.Liao,
H.Wu.
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Ref.
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Cell, 2015,
163,
1138-1152.
[DOI no: ]
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PubMed id
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Abstract
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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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