Cleaved antitrypsin polymers at atomic resolution

alpha(1)-Antitrypsin deficiency, which can lead to both em physema and live r disease, is a result of the accumulation of alpha(1)-antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data sugges ts that alpha(1)-antitrypsin polymers form via insertion of residues from t he reactive center loop of one molecule into the beta-sheet of another. How ever, this long-standing hypothesis has not been confirmed by direct struct ural evidence. Here, we describe the first crystallographic evidence of a b eta-strand linked polymer form of alpha(1)-antitrypsin: the crystal structu re of a cleaved cri-antitrypsin polymer.