THE Z-TYPE VARIATION OF HUMAN ALPHA(1)-ANTITRYPSIN CAUSES A PROTEIN-FOLDING DEFECT

被引：131

作者：

YU, MH

LEE, KN

KIM, J

机构：

[1] Protein Engineering Group, Genetic Engineering Research Institute, Korea Institute of Science and Technology, Taejon, 305-600

[2] Laboratory of Bioorganlc Chemistry, NIDDK, NIH, Bethesda, MD

来源：

NATURE STRUCTURAL BIOLOGY | 1995年 / 2卷 / 05期

关键词：

D O I：

10.1038/nsb0595-363

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Emphysema is often associated with the Z type mutation of alpha(1)-antitrypsin, which causes aggregation of the molecule in the liver and consequent plasma deficiency. The aggregation appears to be due to loop-sheet polymerization, although why the mutant protein polymerizes in vivo is unclear. Here we show that, unlike wild type antitrypsin, which folds in minutes, the folding of Z type alpha(1)-antitrypsin is extremely slow. Once folded, however, the native Z protein shows substantial stability towards urea and incubation at 37 degrees C. The folding defect in Z antitrypsin leads to accumulation of an intermediate and it is the intermediate rather than the native protein which has a high tendency to aggregate.

引用

页码：363 / 367

页数：5

共 30 条

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