一个动力蛋白聚合物的拟原子模型确定了一个依赖于水解的动力冲程。
A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke.
机构信息
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
出版信息
Cell. 2011 Sep 30;147(1):209-22. doi: 10.1016/j.cell.2011.09.003.
The GTPase dynamin catalyzes membrane fission by forming a collar around the necks of clathrin-coated pits, but the specific structural interactions and conformational changes that drive this process remain a mystery. We present the GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2 Å and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 Å. The structures reveal the position and connectivity of dynamin fragments in the assembled structure, showing that G domain dimers only form between tetramers in sequential rungs of the dynamin helix. Using chemical crosslinking, we demonstrate that dynamin tetramers are made of two dimers, in which the G domain of one molecule interacts in trans with the GED of another. Structural comparison of GG(GMPPCP) to the GG transition-state complex identifies a hydrolysis-dependent powerstroke that may play a role in membrane-remodeling events necessary for fission.
GTP 酶 dynamin 通过在网格蛋白包被凹陷的颈部周围形成一个环来催化膜裂变，但驱动这个过程的具体结构相互作用和构象变化仍然是一个谜。我们展示了结合 GMPPCP 的截断人源 dynamin 1 螺旋聚合物在 12.2Å 和一个融合蛋白 GG 的结构，GG 将人源 dynamin 1 的催化 G 结构域连接到其 GTP 酶效应结构域 (GED) 在 2.2Å。这些结构揭示了组装结构中 dynamin 片段的位置和连接性，表明 G 结构域二聚体仅在 dynamin 螺旋的连续梯级中的四聚体之间形成。通过使用化学交联，我们证明 dynamin 四聚体由两个二聚体组成，其中一个分子的 G 结构域与另一个分子的 GED 相互作用。GG(GMPPCP)与 GG 过渡态复合物的结构比较确定了一个依赖于水解的动力冲程，它可能在裂变所需的膜重塑事件中发挥作用。
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