Structure and interactions of the Bacillus subtilis sporulation inhibitor of DNA replication, SirA, with domain I of DnaA.
Structure and interactions of the Bacillus subtilis sporulation inhibitor of DNA replication, SirA, with domain I of DnaA.
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DOI：
10.1111/mmi.12713
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发表时间：
2014-09
影响因子：
3.6
通讯作者：
Wilkinson AJ
中科院分区：
文献类型：
--
作者：
Jameson KH;Rostami N;Fogg MJ;Turkenburg JP;Grahl A;Murray H;Wilkinson AJ
细胞中的染色体拷贝数受到控制，使得DNA复制起始的频率与细胞分裂的频率相匹配。在细菌中，这是通过调节起始蛋白DnaA和排列在复制起点的特定DNA元件之间的相互作用来实现的。DnaA在起点组装，并促进DNA解旋和复制起始复合物的组装。SirA是一种DnaA相互作用蛋白，其抑制二倍体枯草芽孢杆菌细胞中的复制起始，所述细胞致力于导致休眠孢子形成的发育途径。在这里，我们提出的晶体结构的SirA在复杂的N-末端结构域的DnaA揭示异二聚体复合物。这两种蛋白质的相互作用表面是α-螺旋的，主要是非极性侧链包装在疏水界面中。定点诱变实验证实了这两种蛋白质在体外和体内相互作用的重要性。GFP-SirA的定位表明该蛋白质可能通过与DnaA的直接相互作用而在孢子形成细胞中的复制体处积累。DnaA的SirA相互作用表面与来自幽门螺杆菌的DnaA的HobA相互作用表面紧密对应，尽管HobA是DnaA的激活剂而SirA是抑制剂。
Chromosome copy number in cells is controlled so that the frequency of initiation of DNA replication matches that of cell division. In bacteria, this is achieved through regulation of the interaction between the initiator protein DnaA and specific DNA elements arrayed at the origin of replication. DnaA assembles at the origin and promotes DNA unwinding and the assembly of a replication initiation complex. SirA is a DnaA-interacting protein that inhibits initiation of replication in diploid Bacillus subtilis cells committed to the developmental pathway leading to formation of a dormant spore. Here we present the crystal structure of SirA in complex with the N-terminal domain of DnaA revealing a heterodimeric complex. The interacting surfaces of both proteins are α-helical with predominantly apolar side-chains packing in a hydrophobic interface. Site-directed mutagenesis experiments confirm the importance of this interface for the interaction of the two proteins in vitro and in vivo. Localization of GFP–SirA indicates that the protein accumulates at the replisome in sporulating cells, likely through a direct interaction with DnaA. The SirA interacting surface of DnaA corresponds closely to the HobA-interacting surface of DnaA from Helicobacter pylori even though HobA is an activator of DnaA and SirA is an inhibitor.
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影响因子：
10.5
作者：
Leonard AC;Grimwade JE
通讯作者：
Grimwade JE
DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
通过细菌启动器拉伸的DNA促进了复制起源。
影响因子：
64.8
作者：
Duderstadt, Karl E.;Chuang, Kevin;Berger, James M.
通讯作者：
Berger, James M.
影响因子：
4.8
作者：
Abe, Yoshito;Jo, Takaaki;Ueda, Tadashi
通讯作者：
Ueda, Tadashi
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K