Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science, Seoul 02841, South Korea.
Department of Physics, Korea University, Seoul 02841, South Korea.
Nucleic Acids Res. 2018 May 4;46(8):4129-4137. doi: 10.1093/nar/gky200.
Left-handed Z-DNA is an extraordinary conformation of DNA, which can form by special sequences under specific biological, chemical or physical conditions. Human ADAR1, prototypic Z-DNA binding protein (ZBP), binds to Z-DNA with high affinity. Utilizing single-molecule FRET assays for Z-DNA forming sequences embedded in a long inactive DNA, we measure thermodynamic populations of ADAR1-bound DNA conformations in both GC and TG repeat sequences. Based on a statistical physics model, we determined quantitatively the affinities of ADAR1 to both Z-form and B-form of these sequences. We also reported what pathways it takes to induce the B-Z transition in those sequences. Due to the high junction energy, an intermediate B* state has to accumulate prior to the B-Z transition. Our study showing the stable B* state supports the active picture for the protein-induced B-Z transition that occurs under a physiological setting.
左手 Z-DNA 是一种特殊的 DNA 构象，它可以在特定的生物、化学或物理条件下由特殊序列形成。人类 ADAR1 是典型的 Z-DNA 结合蛋白（ZBP），它能与 Z-DNA 高亲和力结合。利用单分子 FRET 测定法对嵌入在长非活性 DNA 中的 Z-DNA 形成序列进行测定，我们测量了 ADAR1 结合的 DNA 构象在 GC 和 TG 重复序列中的热力学种群。基于统计物理模型，我们定量确定了 ADAR1 与这些序列的 Z 型和 B 型的亲和力。我们还报告了它在这些序列中诱导 B-Z 转变的途径。由于高连接能量，在发生 B-Z 转变之前必须积累中间 B状态。我们的研究表明，稳定的 B状态支持在生理环境下发生的蛋白诱导的 B-Z 转变的活跃图景。
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