Journal article

Acid denaturation of alpha(1)-antitrypsin: Characterization of a novel mechanism of serpin polymerization

GL Devlin, MKM Chow, GJ Howlett, SP Bottomley

JOURNAL OF MOLECULAR BIOLOGY | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2002

Abstract

The native serpin architecture is extremely sensitive to mutation and environmental factors. These factors induce the formation of a partially folded species that results in the production of inactive loop-sheet polymers. The deposition of these aggregates in tissue, results in diseases such as liver cirrhosis, thrombosis, angioedema and dementia. In this study, we characterize the kinetics and conformational changes of alpha(1)-antitrypsin polymerization at pH 4 using tryptophan fluorescence, circular dichroism, turbidity changes and thioflavin T binding. These biophysical techniques have demonstrated that polymerization begins with a reversible conformational change that results in partial..

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University of Melbourne Researchers