The mechanism of alpha 1-antitrypsin polymerization probed by fluorescence spectroscopy.

Abstract:

:The polymerization of alpha1-antitrypsin within the hepatic cell leads to alpha1-antitrypsin deficiency. Both the conformational changes and the kinetics of the polymerization process are poorly understood. Here we describe fluorescence experiments investigating the polymerization reaction using the fluorescent probe4, 4'-dianilino-1,1'-binaphthyl-5,5'-disulfonate (bis-ANS) which bound to both native and polymerized alpha1-antitrypsin. Biphasic changes in bis-ANS fluorescence were observed during formation of alpha1-antitrypsin polymers. Initially a rapid increase in fluorescence signal was observed; it was followed by a gradual reduction in fluorescence signal. The first phase is a conformational change in which the A beta-sheet of alpha1-antitrypsin opens, whereas the second phase represents the insertion of the reactive center loop into the A beta-sheet of another molecule and therefore determines the rate of the polymerization process.

journal_name

Arch Biochem Biophys

authors

James EL,Bottomley SP

doi

10.1006/abbi.1998.0751

subject

Has Abstract

pub_date

1998-08-15 00:00:00

pages

296-300

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(98)90751-2

journal_volume

356

pub_type

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