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The molecular species responsible for α 1 ‐antitrypsin deficiency are suppressed by a small molecule chaperone
Author(s) -
Ronzoni Riccardo,
HeyerChauhan Nina,
Fra Annamaria,
Pearce Andrew C.,
Rüdiger Martin,
Miranda Elena,
Irving James A.,
Lomas David A.
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15597
Subject(s) - monoclonal antibody , polymer , small molecule , biophysics , in vivo , chemistry , in vitro , intracellular , molecule , polymerization , biochemistry , secretion , antibody , biology , immunology , organic chemistry , microbiology and biotechnology
The formation of ordered Z α 1 ‐antitrypsin polymers is central to liver disease in α 1 ‐antitrypsin deficiency. The nascent α 1 ‐antitrypsin folds via the M* intermediate to native monomer or becomes incorporated into a soluble polymer that can be secreted, degraded or precipitate as insoluble inclusions. We describe the kinetics of the clearance of Z α 1 ‐antitrypsin polymers and show that they can be abolished with a small molecule preventing the formation of M*.
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