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Aggregation of plasma Z type α 1 ‐antitrypsin suggests basic defect for the deficiency
Author(s) -
Cox D.W.,
Billingsley G.D.,
Callahan J.W.
Publication year - 1986
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(86)80908-5
Subject(s) - alpha (finance) , alpha 1 antitrypsin deficiency , chemistry , protease inhibitor (pharmacology) , blood proteins , protease , plasma , salt bridge , biochemistry , microbiology and biotechnology , biology , enzyme , immunology , physics , medicine , mutant , gene , construct validity , nursing , quantum mechanics , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load , patient satisfaction
The abnormal type of α 1 ‐antitrypsin, PI (protease inhibitor) type Z, is associated with inclusion bodies in the liver, which contain non‐secreted α 1 ‐antitrypsin. Our studies show that Z protein has an inherent tendency to aggregate, even in plasma. Depending upon conditions, from 15 to 70% of the Z protein in plasma was in a high‐ M r form, compared with 1.5% of M type α 1 ‐antitrypsin. The high‐ M r complex in plasma cannot be disaggregated using Triton X detergent or reducing conditions. This increased tendency to aggregate can be explained by the mutation affecting, tertiary structure and salt bridge formation in Z protein. We have observed this same tendency to aggregate for Mmalton α 1 ‐antitrypsin, a rarer variant also associated with a plasma deficiency.