a Faculty of Food and Agricultural Sciences, Department of Food Science and Nutrition , King Saud University , 2460 Riyadh 11451 , Saudi Arabia.
b Department of Biochemistry, College of Science , King Saud University , Riyadh , Saudi Arabia.
J Biomol Struct Dyn. 2018 May;36(6):1550-1565. doi: 10.1080/07391102.2017.1329097. Epub 2017 May 28.
Amyloid fibril formation is responsible for several neurodegenerative diseases and are formed when native proteins misfold and stick together with different interactive forces. In the present study, we have determined the mode of interaction of the anionic surfactant sarkosyl with hen egg white lysozyme (HEWL) [EC No. 3.2.1.17] at two pHs (9.0 and 13.0) and investigated its impact on fibrillogenesis. Our data suggested that sarkosyl is promoting amyloid fibril formation in HEWL at the concentration range between 0.9 and 3.0 mM and no amyloid fibril formation was observed in the concentration range of 3.0-20.0 mM at pH 9.0. The results were confirmed by several biophysical and computational techniques, such as turbidity measurement, dynamic light scattering, Raleigh scattering, ThT fluorescence, intrinsic fluorescence, far-UV CD and atomic force microscopy. Sarkosyl was unable to induce aggregation in HEWL at pH 13.0 as confirmed by turbidity and RLS measurements. HEWL forms larger amyloid fibrils in the presence of 1.6 mM of sarkosyl. The spectroscopic, microscopic and molecular docking data suggest that the negatively charged carboxylate group and 12-carbon hydrophobic tail of sarkosyl stimulate amyloid fibril formation in HEWL via electrostatic and hydrophobic interaction. This study leads to new insight into the process of suppression of fibrillogenesis in HEWL which can be prevented by designing ligands that can retard the electrostatic and hydrophobic interaction between sarkosyl and HEWL.
淀粉样纤维的形成是几种神经退行性疾病的原因，当天然蛋白质错误折叠并相互作用时形成淀粉样纤维。在本研究中，我们确定了阴离子表面活性剂十二烷基硫酸钠（Sarkosyl）与鸡卵清白溶菌酶（HEWL）[EC 编号 3.2.1.17]在两个 pH 值（9.0 和 13.0）下的相互作用模式，并研究了其对纤维形成的影响。我们的数据表明，Sarkosyl 在 0.9-3.0 mM 的浓度范围内促进 HEWL 的淀粉样纤维形成，而在 pH 9.0 时，在 3.0-20.0 mM 的浓度范围内没有观察到淀粉样纤维形成。该结果通过几种生物物理和计算技术得到了证实，例如浊度测量、动态光散射、瑞利散射、ThT 荧光、本征荧光、远紫外 CD 和原子力显微镜。Sarkosyl 不能在 pH 13.0 下诱导 HEWL 聚集，这一点通过浊度和 RLS 测量得到了证实。在 1.6 mM Sarkosyl 的存在下，HEWL 形成更大的淀粉样纤维。光谱学、显微镜学和分子对接数据表明，Sarkosyl 的带负电荷的羧酸盐基团和 12 碳疏水尾通过静电和疏水相互作用刺激 HEWL 中的淀粉样纤维形成。这项研究为抑制 HEWL 纤维形成的过程提供了新的见解，可以通过设计能够延缓 Sarkosyl 和 HEWL 之间静电和疏水相互作用的配体来防止纤维形成。
