Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
J Phys Chem B. 2013 Apr 18;117(15):4003-13. doi: 10.1021/jp4003559. Epub 2013 Apr 9.
Hen egg white lysozyme (HEWL) is widely used as a model protein for amyloid research. In this study, we aim to use Fourier transform infrared (FTIR) spectroscopy to gain new structural insights into amyloid formation of HEWL under heat and acidic condition. We reveal that the fibril-forming solution of HEWL has the capability to form fibril and oligomer with distinct β-sheet configurations under different temperatures. Amyloid fibril with parallel β-sheet configuration is formed at elevated temperature, while oligomer with antiparallel β-sheet configuration is formed at room temperature. The interplay between fibrillation and oligomerization suggests that the two β-sheet aggregates consume the same amyloidogenic materials such as peptide fragments and nicked HEWL due to lysozyme hydrolysis under heat and acidic condition. Temperature-dependent FTIR reveals that the oligomer is unstable at elevated temperature, demonstrating its off-pathway nature. The temperature-dependent formation of parallel and antiparallel β-sheet configurations discovered in lysozyme system is compared with that of amyloid-β and α-synuclein systems and the implication is discussed.
蛋清溶菌酶（HEWL）被广泛用作研究淀粉样蛋白的模型蛋白。在这项研究中，我们旨在使用傅里叶变换红外（FTIR）光谱技术，从结构上深入了解 HEWL 在热和酸性条件下的淀粉样蛋白形成过程。结果表明，HEWL 的原纤维形成溶液在不同温度下具有形成具有不同β-折叠结构的纤维和低聚物的能力。在较高温度下形成平行β-折叠结构的纤维，而在室温下形成反平行β-折叠结构的低聚物。纤维形成和低聚作用的相互作用表明，由于热和酸性条件下溶菌酶的水解，两种β-折叠聚集物消耗相同的淀粉样蛋白形成物质，如肽片段和缺口 HEWL。温度依赖性 FTIR 揭示了在较高温度下低聚物不稳定，表明其偏离了正常途径。溶菌酶系统中发现的平行和反平行β-折叠结构的温度依赖性形成与淀粉样β和α-突触核蛋白系统进行了比较，并讨论了其意义。
