Ultrasonication-dependent production and breakdown lead to minimum-sized amyloid fibrils
Ultrasonication-dependent production and breakdown lead to minimum-sized amyloid fibrils
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DOI：
10.1073/pnas.0901422106
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发表时间：
2009-07-07
影响因子：
11.1
通讯作者：
Goto, Yuji
中科院分区：
文献类型：
--
作者：
Chatani, Eri;Lee, Young-Ho;Goto, Yuji
由于淀粉样蛋白原纤维的不溶性和聚合特性，通常用于分析蛋白质结构和动力学的技术常常受到阻碍。超声波处理可诱导淀粉样蛋白单体溶液形成淀粉样纤维。然而，超声处理可以将预形成的原纤维分解成较短的原纤维。在这里，结合这两种对β（2）-微球蛋白（β（2）-m）（一种负责透析相关淀粉样变性的蛋白质）的相反作用，我们提出超声脉冲可用于制备平均分子量约为1，660，000（140-mer）的最小尺寸的单分散淀粉样蛋白原纤维。最小和单分散的原纤维的生产是通过原纤维生产和断裂之间的竞争下的自由能最小值来实现的。小的均匀纤维将用于表征淀粉样纤维的结构和动力学，推进淀粉样变性的分子理解。
Because of the insolubility and polymeric properties of amyloid fibrils, techniques used conventionally to analyze protein structure and dynamics have often been hampered. Ultrasonication can induce the monomeric solution of amyloidogenic proteins to form amyloid fibrils. However, ultrasonication can break down preformed fibrils into shorter fibrils. Here, combining these 2 opposing effects on beta(2)-microglobulin (beta(2)-m), a protein responsible for dialysis-related amyloidosis, we present that ultrasonication pulses are useful for preparing monodispersed amyloid fibrils of minimal size with an average molecular weight of approximate to 1,660,000 (140-mer). The production of minimal and monodispersed fibrils is achieved by the free energy minimum under competition between fibril production and breakdown. The small homogeneous fibrils will be of use for characterizing the structure and dynamics of amyloid fibrils, advancing molecular understanding of amyloidosis.