Funahashi J, Takano K, Ogasahara K, Yamagata Y, Yutani K
Institute for Protein Research, Osaka University.
J Biochem. 1996 Dec;120(6):1216-23. doi: 10.1093/oxfordjournals.jbchem.a021544.
The physicochemical properties of an amyloidogenic mutant human lysozyme (Ile56Thr) were examined in order to elucidate the mechanism of amyloid formation. The crystal structure of the mutant protein was the same as the wild-type structure, except that the hydroxyl group of the introduced Thr56 formed a hydrogen bond with a water molecule in the interior of the protein. The other physicochemical properties of the mutant protein in the native state were not different from those of the wild-type protein. However, the equilibrium and kinetic stabilities of the mutant protein were remarkably decreased due to the introduction of a polar residue (Thr) in the interior of the molecule. It can be concluded that the amyloid formation of the mutant human lysozyme is due to a tendency to favor (partly or/and completely) denatured structures.
为了阐明淀粉样蛋白形成的机制，对一种淀粉样变性突变型人溶菌酶（Ile56Thr）的物理化学性质进行了研究。突变蛋白的晶体结构与野生型结构相同，只是引入的Thr56的羟基与蛋白质内部的一个水分子形成了氢键。天然状态下突变蛋白的其他物理化学性质与野生型蛋白并无差异。然而，由于在分子内部引入了一个极性残基（Thr），突变蛋白的平衡稳定性和动力学稳定性显著降低。可以得出结论，突变型人溶菌酶的淀粉样蛋白形成是由于倾向于（部分或/和完全）形成变性结构。
