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Fibrillation properties of human α1-acid glycoprotein

Fibrillation properties of human α1-acid glycoprotein

Authors :
Fabio Tanfani
Roberta Galeazzi
Maurizio Baldassarre
Andrea Scirè
Source :
Biochimie. 95:158-166
Publication Year :
2013
Publisher :
Elsevier BV, 2013.

Abstract

Human α(1)-acid glycoprotein (AGP) is a positive acute phase plasma protein containing two disulfide bridges. Structural studies have shown that under specific conditions AGP undergoes aggregation. In this study, we analysed the nature of AGP's aggregates formed under reducing and non-reducing conditions at pH 5.5 and at relatively low temperatures. Thioflavin T and Congo red spectroscopic analyses indicated the presence of cross-β structures in both unreduced and reduced AGP aggregates. In these samples amyloid-like fibrils were detected by transmission electron microscopy. The fibrils are branched and bent and present in very large amount in reduced AGP. Kinetics of AGP fibrillation proceeds without a lag phase and the rate constants of cross-β formation are linearly dependent on AGP concentration and result higher under reducing conditions. The data suggest a possible downhill mechanism of polymerization with a first-order monomer concentration dependence. Bioinformatics tools highlighted an extended region that sheathes one side of the molecule containing aggregation-prone regions. Reducing conditions make the extended region less constricted, allowing greater exposure of aggregation-prone regions, thus explaining the higher propensity of AGP to aggregate and fibrillate.

Details

ISSN :
03009084
Volume :
95
Database :
OpenAIRE
Journal :
Biochimie
Accession number :
edsair.doi...........d6551e233eba6da304318332a9de75e9
Full Text :
https://doi.org/10.1016/j.biochi.2012.09.005