Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, I-33100 Udine, Italy.
J Mol Biol. 2010 Aug 13;401(2):286-97. doi: 10.1016/j.jmb.2010.06.016. Epub 2010 Jun 15.
Renal failure impairs the clearance of beta(2)-microglobulin from the serum, with the result that this protein accumulates in joints under the form of amyloid fibrils. While the molecular mechanism leading to deposition of amyloid in vivo is not totally understood, some organic compounds, such as trifluoroethanol (TFE), are commonly used to promote the elongation of amyloid fibrils in vitro. This article gives some insights into the structural properties and the conformational states of beta(2)-microglobulin in the presence of TFE, using both the wild-type protein and the mutant Trp60Gly. The structure of the native state of the protein is rather insensitive to the presence of the alcohol, but the stability of this state is lowered in comparison to some other conformational states. In particular, a native-like folding intermediate is observed in the presence of moderate concentrations of TFE. Instead, at higher concentrations of the alcohol, the population of a disordered native-unlike state is dominant and correlates with the ability to elongate fibrils.
肾衰竭会降低血清中β2-微球蛋白的清除率，导致这种蛋白质以淀粉样纤维的形式在关节中积累。虽然导致体内淀粉样沉积的分子机制尚未完全阐明，但一些有机化合物，如三氟乙醇（TFE），通常被用于促进体外淀粉样纤维的延伸。本文使用野生型蛋白和突变型 Trp60Gly，探讨了β2-微球蛋白在 TFE 存在下的结构特性和构象状态。在酒精存在下，蛋白质的天然状态结构相当不敏感，但与其他构象状态相比，这种状态的稳定性降低。特别是，在中等浓度的 TFE 存在下，观察到类似天然的折叠中间态。相反，在较高浓度的酒精下，无序的非天然状态占据主导地位，并且与延伸纤维的能力相关。
