Cleaved antitrypsin polymers at atomic resolution Academic Article uri icon

abstract

  • Alpha1-antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of the accumulation of alpha1-antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data suggests that alpha1-antitrypsin polymers form via insertion of residues from the reactive center loop of one molecule into the beta-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 beta-strand linked polymer form of alpha1-antitrypsin: the crystal structure of a cleaved alpha1-antitrypsin polymer.

authors

  • Dunstone, Michelle A
  • Rossjohn, Jamie
  • Feil, Susanne C
  • Parker, Michael W
  • Dai, Weiwen
  • Whisstock, James C
  • Pike, Robert N
  • Bottomley, Stephen P
  • Le Bonniec, Bernard F

publication date

  • March 13, 2000