Crystal structure of human DAAM1 formin homology 2 domain
Crystal structure of human DAAM1 formin homology 2 domain
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DOI：
10.1111/j.1365-2443.2007.01132.x
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发表时间：
2007-11
期刊：
影响因子：
2.1
通讯作者：
M. Yamashita;T. Higashi;S. Suetsugu;Yusuke Sato;Tomoyuki Ikeda;R. Shirakawa;T. Kita;T. Takenawa;H. Horiuchi;S. Fukai;O. Nureki
中科院分区：
文献类型：
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作者：
M. Yamashita;T. Higashi;S. Suetsugu;Yusuke Sato;Tomoyuki Ikeda;R. Shirakawa;T. Kita;T. Takenawa;H. Horiuchi;S. Fukai;O. Nureki
肌动蛋白细丝的重组是细胞运动、细胞间附着和细胞内运输的重要过程。Forin蛋白促进肌动蛋白细丝的成核和延长，因此是这一过程的关键调节因子。福尔明同源2(FH2)结构域形成头尾环状二聚体，并向带刺的末端连续移动。脱发相关形态发生激活剂(DAAM)是一种受Rho调节的形式蛋白，与神经元发育有关。在这里，我们提出了人DAAM1FH2二聚体的晶体结构，其分辨率为2.8。这是哺乳动物福尔明的第一个二聚体结构。人DAAM1的核心结构类似于小鼠mDia1和酵母Bni1p的核心结构，而人DAAM1和酵母Bni1p的FH2二聚体环的取向不同，尽管它们的二聚体相互作用相似。这一差异支持了先前的预测，即福尔敏的二聚体结构在无肌动蛋白状态下具有高度的灵活性。使用DAAM1突变体进行肌动蛋白组装分析的结果表明，连接N-末端结构域和核心区的连接子的长度对活性至关重要。
Reorganization of the actin filament is an essential process for cell motility, cell–cell attachment and intracellular transport. Formin proteins promote nucleation and elongation of the actin filament, and thus are key regulators for this process. The formin homology 2 (FH2) domain forms a head‐to‐tail ring‐shaped dimer, and processively moves towards the barbed end. Dishevelled‐associated activator of morphogenesis (DAAM) is a Rho‐regulated formin implicated in neuronal development. Here, we present the crystal structure of human DAAM1 FH2 dimer at 2.8 Å resolution. This is the first dimeric structure of the mammalian formin. The core structure of human DAAM1 is similar to those of mouse mDia1 and yeast Bni1p, whereas the orientations of the FH2 dimeric rings are different between human DAAM1 and yeast Bni1p, despite their similar dimer interactions. This difference supports the previous prediction that the dimer architecture of the formin is highly flexible in the actin‐free state. The results of the actin assembly assays using the DAAM1 mutants demonstrated that the length of the linker connecting the N‐terminal domain and the core region is crucial for the activity.