Surface residues dynamically organize water bridges to enhance electron transfer between proteins
Surface residues dynamically organize water bridges to enhance electron transfer between proteins
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DOI：
10.1073/pnas.0914457107
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发表时间：
2010-06-29
影响因子：
11.1
通讯作者：
Salahub, Dennis R.
中科院分区：
文献类型：
--
作者：
de la Lande, Aurelien;Babcock, Nathan S.;Salahub, Dennis R.
细胞能量的产生依赖于蛋白质之间的电子转移。在这项理论研究中，我们研究了结构和构象变化对脱氮副冠藻氧化还原蛋白甲胺脱氢酶和氨蓝蛋白之间电子偶联的影响。我们使用分子动力学模拟在40 ns的持续时间内生成组态(以100-fs的间隔采样)，并结合ET途径分析来估计每个组态的ET耦合强度。在野生型络合物中，我们发现最常见的分子构型提供了优越的电子耦合，这是因为给体和受体位置之间始终存在一个氢键的水分子。我们将这种水桥的持续存在归因于受体位置周围由几个疏水残基组成的“分子防波堤”。防波堤支持附近的溶剂组织残留物的功能，通过限制空间受限的ET区域和更动荡的周围散体之间的水分子交换来支持。当防波堤受到突变的影响时，大量的溶剂分子破坏了水桥，导致电子耦合减少，这与最近的实验结果一致。我们的分析表明，除了使蛋白质能够结合和对接外，表面残基还以一致的方式稳定和控制蛋白质间的溶剂动力学。
Cellular energy production depends on electron transfer (ET) between proteins. In this theoretical study, we investigate the impact of structural and conformational variations on the electronic coupling between the redox proteins methylamine dehydrogenase and amicyanin from Paracoccus denitrificans. We used molecular dynamics simulations to generate configurations over a duration of 40 ns (sampled at 100-fs intervals) in conjunction with an ET pathway analysis to estimate the ET coupling strength of each configuration. In the wild-type complex, we find that the most frequently occurring molecular configurations afford superior electronic coupling due to the consistent presence of a water molecule hydrogen-bonded between the donor and acceptor sites. We attribute the persistence of this water bridge to a "molecular breakwater" composed of several hydrophobic residues surrounding the acceptor site. The breakwater supports the function of nearby solvent-organizing residues by limiting the exchange of water molecules between the sterically constrained ET region and the more turbulent surrounding bulk. When the breakwater is affected by a mutation, bulk solvent molecules disrupt the water bridge, resulting in reduced electronic coupling that is consistent with recent experimental findings. Our analysis suggests that, in addition to enabling the association and docking of the proteins, surface residues stabilize and control interprotein solvent dynamics in a concerted way.