ALPHA(1)-ANTITRYPSIN POLYMERIZATION CAN OCCUR BY BOTH LOOP A-SHEET AND C-SHEET MECHANISMS

A number of disease states are attributable to alpha(1)-antitrypsin po lymerisation within the endoplasmic reticulum of hepatocytes and subse quent plasma deficiency. Two distinct mechanisms describing the proces s of alpha(1)-antitrypsin polymerisation have been proposed, the loop A-sheet and C-sheet mechanisms. We report fluorescence studies using a lpha(1)-antitrgpsin covalently modified with pyrene maleimide. These r esults in conjunction with detailed molecular modelling studies, show that alpha(1)-antitrypsin is capable of undergoing both loop A-sheet a nd loop C-sheet mechanisms of polymerisation, depending upon the in vi tro buffer conditions. (C) 1998 Academic Press.