Out-of-plane motions in open sliding clamps: Molecular dynamics simulations of eukaryotic and archaeal proliferating cell nuclear antigen
Out-of-plane motions in open sliding clamps: Molecular dynamics simulations of eukaryotic and archaeal proliferating cell nuclear antigen
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DOI：
10.1073/pnas.0506430102
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发表时间：
2005-09-27
影响因子：
11.1
通讯作者：
Kuriyan, J
中科院分区：
文献类型：
--
作者：
Kazmirski, SL;Zhao, YX;Kuriyan, J
滑动夹是环状多聚体蛋白，包围双链体DNA，并作为移动的DNA结合平台，对于有效的DNA复制和修复至关重要。滑动钳放置在DNA上的钳加载复合物，其中钳相互作用的元素是组织在一个右手螺旋大会。要了解如何平面，环状夹具可能与螺旋相互作用表面的夹具装载机复杂的，我们已经进行了分子动力学模拟滑动夹具（增殖细胞核抗原从芽殖酵母，人类和古细菌物种），其中我们已经删除了三个亚基之一，以释放环闭合的约束。模拟揭示了显着的结构波动对应的横向开放和平面外的扭曲的夹具，这主要是由于弯曲和扭曲的β-片跨越分子间的界面，较小的，但类似的贡献，从β-片跨越分子内的每个亚基内的界面。由于这些β折叠的完整性完好无损，模拟中看到的主要波动是侧向开口和右手螺旋之间的振荡。钳采取右手螺旋构象的趋势意味着一旦打开，钳的构象可以容易地匹配钳加载子亚基的螺旋化，这是识别DNA和随后由钳结合的钳加载子复合物水解ATP所固有的特征。
Sliding clamps are ring-like multimeric proteins that encircle duplex DNA and serve as mobile DNA-bound platforms that are essential for efficient DNA replication and repair. Sliding clamps are placed on DNA by clamp loader complexes, in which the clamp-interacting elements are organized in a right-handed spiral assembly. To understand how the flat, ring-like clamps might interact with the spiral interaction surface of the clamp loader complex, we have performed molecular dynamics simulations of sliding clamps (proliferating cell nuclear antigen from the budding yeast, humans, and an archaeal species) in which we have removed one of the three subunits so as to release the constraint of ring closure. The simulations reveal significant structural fluctuations corresponding to lateral opening and out-of-plane distortions of the clamp, which result principally from bending and twisting of the beta-sheets that span the intermolecular interfaces, with smaller but similar contributions from beta-sheets that span the intramolecular interfaces within each subunit. With the integrity of these beta-sheets intact, the predominant fluctuations seen in the simulations are oscillations between lateral openings and right-handed spirals. The tendency for clamps to adopt a right-handed spiral conformation implies that once opened, the conformation of the clamp can easily match the spiraling of clamp loader subunits, a feature that is intrinsic to the recognition of DNA and subsequent hydrolysis of ATP by the clamp-bound clamp loader complex.