The solvent at antigen-binding site regulated C3d-CR2 interactions through the C-terminal tail of C3d at different ion strengths: insights from molecular dynamics simulation.
The solvent at antigen-binding site regulated C3d-CR2 interactions through the C-terminal tail of C3d at different ion strengths: insights from molecular dynamics simulation.
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DOI：
10.1016/j.bbagen.2016.05.002
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发表时间：
2016-10
期刊：
影响因子：
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通讯作者：
Yan Zhang;Jingjing Guo;Lanlan Li;Xuewei Liu;X. Yao;Huanxiang Liu
中科院分区：
文献类型：
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作者：
Yan Zhang;Jingjing Guo;Lanlan Li;Xuewei Liu;X. Yao;Huanxiang Liu
补体受体2(CR2)和补体成分C3的降解片段C3d之间的相互作用在天然免疫系统和获得性免疫系统之间起着重要的联系作用。由于C3d-CR2相互作用在疫苗和抑制剂设计中的重要性，已经进行了许多研究来研究C3d-CR2相互作用。方法对C3d-CR2络合物进行了分子动力学模拟，并进行了能量和结构分析。结果发现，随着离子强度的增加，带电蛋白质与离子的相互作用减弱，C3d-CR2相互作用减弱。此外，离子强度对抗原结合部位和CR2结合部位也有相似的影响。同时，在不同的离子强度下，Ala17和Gln20会在His133和Glu135介导的激活和非激活状态之间转换。结论我们的结果揭示了离子强度对C3d-CR2相互作用的影响源于水、离子的占比和分布的变化。本研究揭示了离子强度对C3d-CR2相互作用的影响的根源，加深了对它们相互作用的分子机制的理解，对疫苗和小分子抑制剂的设计具有一定的参考价值。
BackgroundThe interactions of complement receptor 2 (CR2) and the degradation fragment C3d of complement component C3 play important links between the innate and adaptive immune systems. Due to the importance of C3d–CR2 interaction in the design of vaccines and inhibitors, a number of studies have been performed to investigate C3d–CR2 interaction. Many studies have indicated C3d–CR2 interactions are ionic strength-dependent.MethodsTo investigate the molecular mechanism of C3d–CR2 interaction and the origin of effects of ionic strength, molecular dynamics simulations for C3d–CR2 complex together with the energetic and structural analysis were performed.ResultsOur results revealed the increased interactions between charged protein and ions weaken C3d–CR2 association, as ionic strengths increase. Moreover, ion strengths have similar effects on antigen-binding site and CR2 binding site. Meanwhile, Ala17 and Gln20 will transform between the activated and non-activated states mediated by His133 and Glu135 at different ion strengths.ConclusionsOur results reveal the origins of the effects of ionic strengths on C3d–CR2 interactions are due to the changes of water, ion occupancies and distributions.General significanceThis study uncovers the origin of the effect of ionic strength on C3d–CR2 interaction and deepens the understanding of the molecular mechanism of their interaction, which is valuable for the design of vaccines and small molecule inhibitors.