Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Colloids Surf B Biointerfaces. 2010 Nov 1;81(1):141-51. doi: 10.1016/j.colsurfb.2010.07.001. Epub 2010 Jul 31.
The research presented here is aimed at examining the effects of sodium dodecyl sulfate on the aggregative behavior of hen egg-white lysozyme at pH 2.0. Through various spectroscopic techniques, dynamic light scattering, and electron microscopy, we first demonstrated that SDS exhibited a biphasic effect on lysozyme fibrillation. The presence of SDS at higher concentrations (e.g., 0.25, 5.00, or 20.00 mM SDS) was found to suppress fibril formation of lysozyme whereas fibrillogenic lysozyme-SDS ensemble containing beta-sheet-rich conformation was observed upon the addition of lower concentrations of SDS (e.g., 0.00, 0.06, or 0.1mM SDS). Next, our equilibrium urea-unfolding data revealed that lysozyme samples with higher SDS concentrations showed superior thermodynamic stabilities over the ones with no or lower levels of SDS. Finally, the correlation between SDS concentration and lysozyme aggregative/fibrillogenic propensity and the underlying interacting mechanism were further explored using surface tensiometry and isothermal titration calorimetry. We believe the outcome from this work may not only help decipher the molecular mechanism of amyloid fibrillation, but also shed light on a rational design of potential therapeutic strategies for amyloid pathology.
本研究旨在探讨十二烷基硫酸钠(SDS)在 pH 2.0 下对鸡卵清白溶菌酶聚集行为的影响。通过各种光谱技术、动态光散射和电子显微镜,我们首先证明 SDS 对溶菌酶的纤维化表现出两相作用。在较高浓度(例如 0.25、5.00 或 20.00 mM SDS)下存在 SDS 时,发现其抑制溶菌酶的纤丝形成,而在添加较低浓度的 SDS(例如 0.00、0.06 或 0.1mM SDS)时,观察到富含β-折叠构象的纤丝形成溶菌酶-SDS 聚集体。接下来,我们的平衡脲解折叠数据表明,具有较高 SDS 浓度的溶菌酶样品比没有或较低 SDS 水平的样品具有更高的热力学稳定性。最后,使用表面张力法和等温滴定量热法进一步探讨了 SDS 浓度与溶菌酶聚集/纤维化倾向之间的相关性及其潜在的相互作用机制。我们相信这项工作的结果不仅有助于阐明淀粉样纤维形成的分子机制,还为淀粉样病理的潜在治疗策略的合理设计提供了启示。