PDI and glutathione‐mediated reduction of the glutathionylated variant of human lysozyme

FEBS Letters

Inaka, Koji¹  Taniyama, Yoshio¹  Hayano, Toshiya¹  Matsushima, Masaaki¹  Kikuchi, Masakazu¹  Miki, Kunio²  Otsu, Mieko¹ 

[1] Protein Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565, Japan;Research Laboratory of Resources Utilization, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 227, Japan

关键词: Protein disulfide isomerase;    Protein folding;    Glutathione;    Lysozyme;   

DOI  :  10.1016/0014-5793(93)80993-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A mutant human lysozyme, designated as C77A-a, in which glutathione is bound to Cys95, has been shown to mimic an intermediate in the formation of a disulfide bond during folding of human (h)-lysozyme. Protein disulfide isomerase (PDI), which is believed to catalyze disulfide bond formation and associated protein folding in the endoplasmic reticulum, attacked the glutathionylated h-lysozyme C77A-a to dissociate the glutathione molecule. Structural analyses showed that the protein is folded and that the structure around the disulfide bond, buried in a hydrophobic core, between the protein and the bound glutathione is fairly rigid. Thioredoxin, which has higher reducing activity of protein disulfides than PDI, catalyzed the reduction with lower efficiency. These results strongly suggest that PDI can catalyze the disulfide formation in intermediates with compact structure like the native states in the later step of in vivo protein folding.

【 授权许可】

Unknown