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PDBsum entry 5kbj
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Transcription/DNA
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PDB id
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5kbj
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References listed in PDB file
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Key reference
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Title
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Mechanism of staphylococcal multiresistance plasmid replication origin assembly by the repa protein.
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Authors
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M.A.Schumacher,
N.K.Tonthat,
S.M.Kwong,
N.B.Chinnam,
M.A.Liu,
R.A.Skurray,
N.Firth.
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Ref.
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Proc Natl Acad Sci U S A, 2014,
111,
9121-9126.
[DOI no: ]
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PubMed id
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Abstract
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The staphylococcal multiresistance plasmids are key contributors to the alarming
rise in bacterial multidrug resistance. A conserved replication initiator, RepA,
encoded on these plasmids is essential for their propagation. RepA proteins
consist of flexibly linked N-terminal (NTD) and C-terminal (CTD) domains.
Despite their essential role in replication, the molecular basis for RepA
function is unknown. Here we describe a complete structural and functional
dissection of RepA proteins. Unexpectedly, both the RepA NTD and CTD show
similarity to the corresponding domains of the bacterial primosome protein,
DnaD. Although the RepA and DnaD NTD both contain winged helix-turn-helices, the
DnaD NTD self-assembles into large scaffolds whereas the tetrameric RepA NTD
binds DNA iterons using a newly described DNA binding mode. Strikingly,
structural and atomic force microscopy data reveal that the NTD tetramer
mediates DNA bridging, suggesting a molecular mechanism for origin handcuffing.
Finally, data show that the RepA CTD interacts with the host DnaG primase, which
binds the replicative helicase. Thus, these combined data reveal the molecular
mechanism by which RepA mediates the specific replicon assembly of
staphylococcal multiresistant plasmids.
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