So Masatomo, Ishii Akira, Hata Yasuko, Yagi Hisashi, Naiki Hironobu, Goto Yuji
Institute for Protein Research, Osaka University , Osaka 565-0871, Japan.
Faculty of Medical Science, University of Fukui , Fukui 910-1193, Japan.
Langmuir. 2015 Sep 15;31(36):9973-82. doi: 10.1021/acs.langmuir.5b02186. Epub 2015 Aug 28.
Although various natural and synthetic compounds have been shown to accelerate or inhibit the formation of amyloid fibrils, the mechanisms by which they achieve these adverse effects in a concentration-dependent manner currently remain unclear. Sodium dodecyl sulfate (SDS), one of the compounds that has adverse effects on fibrillation, is the most intensively studied. Here we examined the effects of a series of detergents including SDS on the amyloid fibrillation of β2-microglobulin at pH 7.0, a protein responsible for dialysis-related amyloidosis. In all the detergents examined (i.e., SDS, sodium decyl sulfate, sodium octyl sulfate, and sodium deoxycholate), amyloid fibrillation was accelerated and inhibited at concentrations near the critical micelle concentration (CMC) and higher than CMC, respectively. The most stable conformation changed from monomers with a β-structure to amyloid fibrils with a β-structure and then to α-helical complexes with micelles with an increase in detergent concentrations. These results suggest that competition between supersaturation-limited fibrillation and unlimited mixed micelle formation between proteins and micelles underlies the detergent concentration-dependent complexity of amyloid fibrillation.
尽管各种天然和合成化合物已被证明可加速或抑制淀粉样纤维的形成，但其以浓度依赖方式产生这些不利影响的机制目前仍不清楚。十二烷基硫酸钠（SDS）是对纤维形成有不利影响的化合物之一，也是研究最为深入的。在此，我们研究了包括SDS在内的一系列去污剂对β2-微球蛋白在pH 7.0时淀粉样纤维形成的影响，β2-微球蛋白是一种与透析相关淀粉样变性有关的蛋白质。在所有检测的去污剂（即SDS、癸基硫酸钠、辛基硫酸钠和脱氧胆酸钠）中，淀粉样纤维形成在接近临界胶束浓度（CMC）时加速，而在高于CMC时受到抑制。随着去污剂浓度的增加，最稳定构象从具有β结构的单体变为具有β结构的淀粉样纤维，然后变为与胶束形成的α-螺旋复合物。这些结果表明，过饱和限制的纤维形成与蛋白质和胶束之间无限制的混合胶束形成之间的竞争是去污剂浓度依赖性淀粉样纤维形成复杂性的基础。
