Powers Evan T, Powers David L
Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
Biophys J. 2008 Jan 15;94(2):379-91. doi: 10.1529/biophysj.107.117168. Epub 2007 Sep 21.
The formation of protein fibrils, and in particular amyloid fibrils, underlies many human diseases. Understanding fibril formation mechanisms is important for understanding disease pathology, but fibril formation kinetics can be complicated, making the relationship between experimental observables and specific mechanisms unclear. Here we examine one often-proposed fibril formation mechanism, nucleated polymerization with off-pathway aggregation. We use the characteristics of this mechanism to derive three tests that can be performed on experimental data to identify it. We also find that this mechanism has an especially striking feature: although increasing protein concentrations generally cause simple nucleated polymerizations to reach completion faster, they cause nucleated polymerizations with off-pathway aggregation to reach completion more slowly when the protein concentration becomes too high.
蛋白质原纤维，尤其是淀粉样原纤维的形成是许多人类疾病的基础。了解原纤维形成机制对于理解疾病病理学很重要，但原纤维形成动力学可能很复杂，使得实验观测值与特定机制之间的关系不明确。在这里，我们研究一种经常被提出的原纤维形成机制，即伴有旁路聚集的成核聚合。我们利用该机制的特征推导出三项可以对实验数据进行的测试，以识别该机制。我们还发现该机制有一个特别显著的特征：尽管提高蛋白质浓度通常会使简单的成核聚合更快完成，但当蛋白质浓度过高时，它们会使伴有旁路聚集的成核聚合完成得更慢。
