Graduate School of Science , Nagoya University , Furo-cho, Chikusa-ku, Nagoya 464-8602 , Japan.
Institute of Genetics and Molecular and Cellular Biology , University of Strasbourg , 1 rue Laurent Fries Parc d'Innovation , 67404 Illkirch , Cedex, France.
J Phys Chem B. 2019 Jan 31;123(4):768-775. doi: 10.1021/acs.jpcb.8b10489. Epub 2019 Jan 16.
The effects of ligand binding on an oxygen sensor protein, FixLH, were investigated by molecular dynamics simulation. To illustrate the network of residue interactions in the deoxy, oxy, and carbomonoxy states of FixLH, we employed the energy exchange network (EEN) model in which residue interactions were evaluated in terms of local transport coefficients of energy flow. As a result, the difference map of EEN between the deoxy and oxy (deoxy and carbomonooxy) states clearly demonstrated the allosteric transition, although the structural changes by ligand binding are small. It is known that the FixLH forms a homodimer in solution, although neither O nor CO binding exhibits cooperativity. Therefore, we conjectured that the primary event after ligand binding occurs essentially at the monomer level, and it is subsequently followed by quaternary structural changes. The difference EEN maps showed that two regions, (A) the junction between the coiled-coil linker and the sensor domain and (B) the potential dimer interface, experienced considerable change of the energy-transport coefficients, indicating that these two regions play important roles in quaternary structural changes and signal transduction in response to ligand binding.
通过分子动力学模拟研究了配体结合对氧传感器蛋白 FixLH 的影响。为了说明 FixLH 的脱氧、氧合和碳氧合状态下残基相互作用的网络，我们采用了能量交换网络（EEN）模型，该模型根据能量流的局部输运系数来评估残基相互作用。结果表明，EEN 的氧合态与脱氧态（脱氧态与碳氧合态）之间的差异图谱清楚地表明了变构转变，尽管配体结合引起的结构变化很小。众所周知，FixLH 在溶液中形成同源二聚体，尽管 O 和 CO 结合都不表现出协同性。因此，我们推测配体结合后，主要事件基本上发生在单体水平，随后发生四级结构变化。差异 EEN 图谱显示，两个区域（A）卷曲螺旋接头和传感器结构域之间的连接处和（B）潜在的二聚体界面，经历了能量输运系数的显著变化，表明这两个区域在四级结构变化和信号转导中起着重要作用响应配体结合。
