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PDBsum entry 3os2
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Recombination/DNA
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PDB id
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3os2
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References listed in PDB file
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Key reference
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Title
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The mechanism of retroviral integration from X-Ray structures of its key intermediates.
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Authors
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G.N.Maertens,
S.Hare,
P.Cherepanov.
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Ref.
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Nature, 2010,
468,
326-329.
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PubMed id
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Abstract
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To establish productive infection, a retrovirus must insert a DNA replica of its
genome into host cell chromosomal DNA. This process is operated by the intasome,
a nucleoprotein complex composed of an integrase tetramer (IN) assembled on the
viral DNA ends. The intasome engages chromosomal DNA within a target capture
complex to carry out strand transfer, irreversibly joining the viral and
cellular DNA molecules. Although several intasome/transpososome structures from
the DDE(D) recombinase superfamily have been reported, the mechanics of target
DNA capture and strand transfer by these enzymes remained unclear. Here we
report crystal structures of the intasome from prototype foamy virus in complex
with target DNA, elucidating the pre-integration target DNA capture and
post-catalytic strand transfer intermediates of the retroviral integration
process. The cleft between IN dimers within the intasome accommodates
chromosomal DNA in a severely bent conformation, allowing widely spaced IN
active sites to access the scissile phosphodiester bonds. Our results resolve
the structural basis for retroviral DNA integration and provide a framework for
the design of INs with altered target sequences.
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