Cleaved antitrypsin polymers at atomic resolution

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

Research output: Contribution to journalArticleResearchpeer-review

80 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)417-420
Number of pages4
JournalProtein Science
Volume9
Issue number2
Publication statusPublished - 13 Mar 2000

Keywords

  • α-antitrypsin deficiency
  • Conformational disease
  • Polymerization
  • X-ray crystallography

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