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PDBsum entry 6dbr
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Recombination/DNA
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PDB id
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6dbr
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References listed in PDB file
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Key reference
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Title
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Dna melting initiates the rag catalytic pathway.
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Authors
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H.Ru,
W.Mi,
P.Zhang,
F.W.Alt,
D.G.Schatz,
M.Liao,
H.Wu.
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Ref.
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Nat Struct Mol Biol, 2018,
25,
732-742.
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PubMed id
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Abstract
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The mechanism for initiating DNA cleavage by DDE-family enzymes, including the
RAG endonuclease, which initiates V(D)J recombination, is not well understood.
Here we report six cryo-EM structures of zebrafish RAG in complex with one or
two intact recombination signal sequences (RSSs), at up to 3.9-Å resolution.
Unexpectedly, these structures reveal DNA melting at the heptamer of the RSSs,
thus resulting in a corkscrew-like rotation of coding-flank DNA and the
positioning of the scissile phosphate in the active site. Substrate binding is
associated with dimer opening and a piston-like movement in RAG1, first outward
to accommodate unmelted DNA and then inward to wedge melted DNA. These
precleavage complexes show limited base-specific contacts of RAG at the
conserved terminal CAC/GTG sequence of the heptamer, thus suggesting
conservation based on a propensity to unwind. CA and TG overwhelmingly dominate
terminal sequences in transposons and retrotransposons, thereby implicating a
universal mechanism for DNA melting during the initiation of retroviral
integration and DNA transposition.
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