Dynamic Equilibria of Short-Range Electrostatic Interactions at Molecular Interfaces of Protein-DNA Complexes.
Dynamic Equilibria of Short-Range Electrostatic Interactions at Molecular Interfaces of Protein-DNA Complexes.
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DOI：
10.1021/acs.jpclett.5b01134
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发表时间：
2015-07-16
期刊：
影响因子：
--
通讯作者：
Iwahara J
中科院分区：
文献类型：
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作者：
Chen C;Esadze A;Zandarashvili L;Nguyen D;Montgomery Pettitt B;Iwahara J
分子间离子对（盐桥）对蛋白质-DNA缔合至关重要。对于两个蛋白质-DNA复合物，我们证明了蛋白质侧链NH 3+和DNA磷酸基团的离子对进行不同状态之间的动态转换，其中带电部分是直接接触或分离的水。虽然复合物的晶体结构只显示一些界面赖氨酸侧链的溶剂分离离子对（SIP）状态，但我们的NMR氢键标量耦合数据清楚地表明相同残基的接触离子对（CIP）状态的存在。0.6 μs分子动力学（MD）模拟证实了CIP和SIP状态之间的动态转变。这种行为与我们的核磁共振顺序参数和赖氨酸侧链的标量偶联数据一致。使用MD轨迹，我们还分析了CIP-SIP平衡的自由能。这项工作说明了蛋白质识别DNA的短程静电相互作用的动态性质。
Intermolecular ion pairs (salt bridges) are crucial for protein–DNA association. For two protein–DNA complexes, we demonstrate that the ion pairs of protein side-chain NH3+ and DNA phosphate groups undergo dynamic transitions between distinct states in which the charged moieties are either in direct contact or separated by water. While the crystal structures of the complexes show only the solvent-separated ion pair (SIP) state for some interfacial lysine side chains, our NMR hydrogen-bond scalar coupling data clearly indicate the presence of the contact ion pair (CIP) state for the same residues. The 0.6-μs molecular dynamics (MD) simulations confirm dynamic transitions between the CIP and SIP states. This behavior is consistent with our NMR order parameters and scalar coupling data for the lysine side chains. Using the MD trajectories, we also analyze the free energies of the CIP–SIP equilibria. This work illustrates the dynamic nature of short-range electrostatic interactions in DNA recognition by proteins.