Multiscale evaluation of pore curvature effects on protein structure in nanopores
Multiscale evaluation of pore curvature effects on protein structure in nanopores
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纳米孔中孔曲率对蛋白质结构影响的多尺度评估
DOI：
10.1039/c3tb21714k
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发表时间：
2014
影响因子：
7
通讯作者：
Su Zhi-Guo
中科院分区：
文献类型：
--
作者：
Hao Dong-Xia;Huang Yong-Dong;Wang Kang;Wei Yu-Ping;Zhou Wei-Qing;Li Juan;Ma Guang-Hui;Su Zhi-Guo
纳米孔中的蛋白质结构是生物技术和材料科学中多孔底物利用的重要决定因素。迄今为止，孔曲率诱导蛋白质结合和展开的准确残基细节仍然未知。本文采用色谱法、核磁共振氢氘交换、共聚焦扫描和分子对接模拟等多尺度综合方法，获得了孔径和曲率诱导的蛋白质吸附信息。以14 ~ 120 nm范围内的溶菌酶微球和聚苯乙烯微球为模型。随着孔径的增大，结合的溶菌酶呈现出明显的保留减少、展开减少和相互作用位点减少的趋势。然而，这种显著的孔隙曲率与蛋白质大小之间的依赖关系仅存在于与蛋白质大小相当的有限微孔范围内。通过计算溶菌酶与表面结合的模型，上述事件背后的机制可归因于由孔隙曲率和大小变化决定的不同蛋白质相互作用区域。同时对另一种曲率相反的纳米颗粒表面进行了计算和比较，结果表明，其规律相似，但方向相反，且存在这样的临界尺寸。这些对曲面界面上蛋白质的研究可能最终有助于指导新型多孔材料的设计，并有助于从分子库中区分目标蛋白质。
Protein structure in nanopores is an important determinant in porous substrate utilization in biotechnology and materials science. To date, accurate residue details of pore curvature induced protein binding and unfolding were still unknown. Here, a multiscale ensemble of chromatography, NMR hydrogen and deuterium (H/D) exchange, confocal scanning and molecular docking simulations was combined to obtain the protein adsorption information induced by pore size and curvature. Lysozyme and polystyrene microspheres within pores in the 14–120 nm range were utilized as models. With pore size increasing, the bound lysozyme presented a tendency of significantly decreased retention, less unfolding and fewer interacted sites. However, such a significant dependence between pore curvature and protein size only existed in a limited micro-pore range comparable to protein sizes. The mechanism behind the above events could be attributed to the diverse protein interaction area determined by pore curvature and size change, by models calculating the binding of lysozyme onto surfaces. Another surface of opposite curvature for nanoparticles was also calculated and compared, the rules were similar but with opposite direction and such a critical size also existed. These studies of proteins on curved interfaces may ultimately help to guide the design of novel porous materials and assist in the discrimination of the target protein from molecular banks.