Cleaved antitrypsin polymers at atomic resolution

MA Dunstone, W Dai, JC Whisstock, J Rossjohn… - Protein …, 2000 - cambridge.org
MA Dunstone, W Dai, JC Whisstock, J Rossjohn, RN Pike, SC Feil, BF Le Bonniec…
Protein Science, 2000cambridge.org
α1-Antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of
the accumulation of α1-antitrypsin polymers within the hepatocyte. A wealth of biochemical
and biophysical data suggests that α1-antitrypsin polymers form via insertion of residues
from the reactive center loop of one molecule into the β-sheet of another. However, this long-
standing hypothesis has not been confirmed by direct structural evidence. Here, we describe
the first crystallographic evidence of a β-strand linked polymer form of α1-antitrypsin: the …
α1-Antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of the accumulation of α1-antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data suggests that α1-antitrypsin polymers form via insertion of residues from the reactive center loop of one molecule into the β-sheet of another. However, this long-standing hypothesis has not been confirmed by direct structural evidence. Here, we describe the first crystallographic evidence of a β-strand linked polymer form of α1-antitrypsin: the crystal structure of a cleaved α1-antitrypsin polymer.
Cambridge University Press