Biochemical implications of a three-dimensional model of monomeric actin bound to magnesium-chelated ATP
Biochemical implications of a three-dimensional model of monomeric actin bound to magnesium-chelated ATP
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DOI：
10.1016/j.str.2006.11.005
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发表时间：
2007-01-01
期刊：
影响因子：
5.7
通讯作者：
Chance, Mark R.
中科院分区：
文献类型：
--
作者：
Takamoto, Keiji;Kamal, J. K. Amisha;Chance, Mark R.
肌动蛋白结构在生物学中引起了人们的浓厚兴趣，因为它在细胞功能和运动中具有重要意义，而细胞功能和运动是由肌动蛋白单体-丝状互变在各种发育和疾病状态下的空间和时间调节介导的。尽管存在这种兴趣，但许多功能上重要的肌动蛋白形式的结构仍然未能进行高分辨率分析。由于肌动蛋白单体倾向于组装成丝，镁结合肌动蛋白单体的结构分析已被证明是困难的，而具有多种配体以阻止聚合的肌动蛋白的高分辨率结构已经相当成功。在这项工作中，我们结合计算方法和我们之前发表的实验足迹数据，提供了 MgATP-肌动蛋白单体的高分辨率结构模型。这项研究的主要结论是，由子结构域 2 和 4 定义的核苷酸结合裂缝的结构基本上是封闭的，数据预测两个子结构域之间存在特定的接触。
Actin structure is of intense interest in biology due to its importance in cell function and motility mediated by the spatial and temporal regulation of actin monomer-filament interconversions in a wide range of developmental and disease states. Despite this interest, the structure of many functionally important actin forms has eluded high-resolution analysis. Due to the propensity of actin monomers to assemble into filaments structural analysis of Mg-bound actin monomers has proven difficult, whereas high-resolution structures of actin with a diverse array of ligands that preclude polymerization have been quite successful. In this work, we provide a high-resolution structural model of the MgATP-actin monomer using a combination of computational methods and experimental foot-printing data that we have previously published. The key conclusion of this study is that the structure of the nucleotide binding cleft defined by subdomains 2 and 4 is essentially closed, with specific contacts between two subdomains predicted by the data.