Structure of the human RECQ1 helicase reveals a putative strand-separation pin
Structure of the human RECQ1 helicase reveals a putative strand-separation pin
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DOI：
10.1073/pnas.0806908106
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发表时间：
2009-01-27
影响因子：
11.1
通讯作者：
Gileadi, Opher
中科院分区：
文献类型：
--
作者：
Pike, Ashley C. W.;Shrestha, Binesh;Gileadi, Opher
RecQ 样解旋酶在人类基因组中包含 5 个成员，对于维持基因组完整性非常重要。我们展示了带有 Mg-ADP 的人类 RECQ1 蛋白截短形式的晶体结构。截短的蛋白质在 DNA 分叉解旋中具有活性，但缺乏全长酶的其他活性：破坏霍利迪连接和 DNA 链退火。人类 RECQ1 的结构与大肠杆菌 RecQ 的结构相似，但有一些重要的差异。所有结构域都是保守的，包括 2 个 RecA 样域和 RecQ 特异性锌结合域和翼状螺旋 (WH) 域。然而，WH 结构域的定位方向与大肠杆菌酶的方向不同。我们发现 WH 结构域的一个突出的 β 发夹对于 DNA 链分离至关重要，这可能类似于其他 DNA 解旋酶的 DNA 链分离特征。这种发夹在大肠杆菌酶中明显较短，并且不是其解旋酶活性所必需的，这表明 RecQ 家族成员的作用模式之间存在显着差异。
RecQ-like helicases, which include 5 members in the human genome, are important in maintaining genome integrity. We present a crystal structure of a truncated form of the human RECQ1 protein with Mg-ADP. The truncated protein is active in DNA fork unwinding but lacks other activities of the full-length enzyme: disruption of Holliday junctions and DNA strand annealing. The structure of human RECQ1 resembles that of Escherichia coli RecQ, with some important differences. All structural domains are conserved, including the 2 RecA-like domains and the RecQ-specific zinc-binding and winged-helix (WH) domains. However, the WH domain is positioned at a different orientation from that of the E. coli enzyme. We identify a prominent beta-hairpin of the WH domain as essential for DNA strand separation, which may be analogous to DNA strand-separation features of other DNA helicases. This hairpin is significantly shorter in the E. coli enzyme and is not required for its helicase activity, suggesting that there are significant differences between the modes of action of RecQ family members.