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Nat Struct Biol. 1995 May;2(5):363-7.

The Z type variation of human alpha 1-antitrypsin causes a protein folding defect.

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Genetic Engineering Research Institute, Korea Institute of Science and Technology, Yusong, Taejon.


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.

[Indexed for MEDLINE]

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