α1-antitrypsin polymerisation can occur by both loop A and C sheet mechanisms

A number of disease states are attributable to alpha(1)-antitrypsin polymerisation within the endoplasmic reticulum of hepatocytes and subsequent plasma deficiency. Two distinct mechanisms describing the process of alpha(1)-antitrypsin polymerisation have been proposed, the loop A-sheet and C-sheet mechanisms. We report fluorescence studies using alpha(1)-antitrgpsin covalently modified with pyrene maleimide. These results in conjunction with detailed molecular modelling studies, show that alpha(1)-antitrypsin is capable of undergoing both loop A-sheet and loop C-sheet mechanisms of polymerisation, depending upon the in vitro buffer conditions. (C) 1998 Academic Press.