Structural synergy and molecular crosstalk between bacterial helicase loaders and replication initiators.

Structural synergy and molecular crosstalk between bacterial helicase loaders and replication initiators.
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DOI:
10.1016/j.cell.2008.09.058
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发表时间:
2008-11-14
期刊:
影响因子:
64.5
通讯作者:
Berger, James M.
Berger, James M.
中科院分区:
生物学1区
文献类型:
--
作者:
Mott, Melissa L.;Erzberger, Jan P.;Coons, Mary M.;Berger, James M.

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The loading of oligomeric helicases onto replication origins marks an essential step in replisome assembly. In cells, dedicated AAA+ ATPases regulate loading, however, the mechanism by which these factors help recruit and deposit helicases has remained unclear. To better understand this process, we determined the structure of the ATPase region of the bacterial helicase loader DnaC from Aquifex aeolicus to 2.7 Å resolution. The structure shows that DnaC is a close paralog of the bacterial replication initiator, DnaA, that unexpectedly forms a right-handed helical assembly similar to the quaternary state adopted by ATP-bound DnaA. Complementation and ssDNA-binding assays validate the importance of homomeric DnaC interactions, while pull-down experiments show that the AAA+ domains of DnaC and DnaA interact in a nucleotide-dependent manner. These findings implicate DnaC as a molecular adaptor that uses ATP-activated DnaA as a docking site for regulating the recruitment and correct spatial deposition of the DnaB helicase onto origins.
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