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Amyloid fibril formation by bovine alpha(1)-acid glycoprotein in a reducing environment: The role of disulfide bridges on the observed aggregation kinetics
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Number of Authors: 4
2015 (English)In: Biochimie, ISSN 0300-9084, E-ISSN 1638-6183, Vol. 118, 244-252 p.Article in journal (Refereed) Published
Abstract [en]

Bovine alpha(1)-acid glycoprotein (bAGP), a thermostable counterpart of its human homologue, is a positive acute phase protein involved in binding and transportation of a large number of bin-active molecules and drugs across the body. We have investigated the effect of low pH and reducing conditions on the structure of the protein and found that it aggregates at high temperatures. The aggregates show a fibrillar structure when observed with electron microscopy. Aggregation assays using the amyloid-specific dye Thioflavin T show the presence of a lag phase which was neither abolished nor shortened when seeds were added. A priori reduction of the two disulfide bridges of bAGP, on the other hand, abolished the lag phase and reveals a connection between the kinetics of reduction and aggregation. We provide a kinetic interpretation and the corresponding rate laws allowing to model the process of fibril formation by bAGP under reducing conditions. Our interpretation allows to assess the role of disulfide bridges on the fibrillation kinetics of bAGP and can provide a more accurate interpretation of the fibrillation kinetics of other amyloidogenic proteins containing disulfide bridges.

Place, publisher, year, edition, pages
2015. Vol. 118, 244-252 p.
Keyword [en]
alpha(1)-acid glycoprotein, Orosomucoid, Infrared spectroscopy, Protein aggregation, Amyloid-like fibrils, Disulfide bridge
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-125009DOI: 10.1016/j.biochi.2015.09.026ISI: 000365062200027PubMedID: 26409898OAI: oai:DiVA.org:su-125009DiVA: diva2:893375
Available from: 2016-01-12 Created: 2016-01-07 Last updated: 2016-01-12Bibliographically approved

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Baldassarre, Maurizio
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Department of Biochemistry and Biophysics
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