Structural Studies of Alpha-1-Antitrypsin in Native and Polyper State

Alpha- 1-Antitrypsin (AAT) is a member of a superfamily of serine proteinase inhibitors, and consists of 394 amino acids, which form three ß-sheets (A-C), nine -helices (A-I) and a reactive center loop. Point mutation and environmental factors can destabilize ß-Sheet A and distort the structure of the protein to allow a unique protein-protein interaction residues of one serpin molecule to be inserted into the ß-sheet A of another, that loop-sheet polymerization will be formed. These polymers accumulate within the endoplasmic reticulum of the hepatocyte fromed inclusion bodies which causes a range of diseases such as: neonatal hepatits, Juvenil cirrhosis and adult hepatocellular carcinoma, emphysema, and thrombosis. In this work it has been studied the conformational factors (Temperature, concentration and incubation time) on AAT polymerization. Using spectrofluremetery, turbidometery, circular dichroism, and flourometeric methods. The results of nondenaturing polyacrylamid gel electrophoresis confirmed several steps in polymerization, in presence of above mentioned environmental factors. Accordingly native of AAT migrated as a monomeric band where formed multimeric species of loop-sheet polymer seen. In conclusion it has been established that incubation temprature, concentration can cause essential variation in the structure of AAT, and leads to its di,tri,oligo and polymerization.In addition, the polymerization occures with different rate and this structural changs accounts the activity of AAT.