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Int. J. Mol. Sci. 2013, 14(9), 18362-18384; doi:10.3390/ijms140918362

The Role of Initial Oligomers in Amyloid Fibril Formation by Human Stefin B

1
Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana 1000, Slovenia
2
Jožef Stefan's International Postgraduate School (IPS), Ljubljana 1000, Slovenia
3
Department of Gene Technology, Tallinn University of Technology, Tallinn 12618, Estonia
4
Department of Biotechnology and System Biology, National Institute of Biology, Ljubljana 1000, Slovenia
5
Faculty of Mathematics and Physics, University of Ljubljana, Ljubljana 1000, Slovenia
6
Department of Condensed Matter Physics, Jožef Stefan Institute, Ljubljana 1000, Slovenia
7
Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK
*
Authors to whom correspondence should be addressed.
Received: 6 June 2013 / Revised: 21 August 2013 / Accepted: 22 August 2013 / Published: 5 September 2013
(This article belongs to the collection Protein Folding)
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Abstract

Oligomers are commonly observed intermediates at the initial stages of amyloid fibril formation. They are toxic to neurons and cause decrease in neural transmission and long-term potentiation. We describe an in vitro study of the initial steps in amyloid fibril formation by human stefin B, which proved to be a good model system. Due to relative stability of the initial oligomers of stefin B, electrospray ionization mass spectrometry (ESI MS) could be applied in addition to size exclusion chromatography (SEC). These two techniques enabled us to separate and detect distinguished oligomers from the monomers: dimers, trimers, tetramers, up to decamers. The amyloid fibril formation process was followed at different pH and temperatures, including such conditions where the process was slow enough to detect the initial oligomeric species at the very beginning of the lag phase and those at the end of the lag phase. Taking into account the results of the lower-order oligomers transformations early in the process, we were able to propose an improved model for the stefin B fibril formation.
Keywords: human stefin B; cystatins; protein aggregation; prefibrillar oligomers; mechanism of amyloid fibril formation; ESI MS; SEC; lag phase human stefin B; cystatins; protein aggregation; prefibrillar oligomers; mechanism of amyloid fibril formation; ESI MS; SEC; lag phase
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Taler-Verčič, A.; Kirsipuu, T.; Friedemann, M.; Noormägi, A.; Polajnar, M.; Smirnova, J.; Žnidarič, M.T.; Žganec, M.; Škarabot, M.; Vilfan, A.; Staniforth, R.A.; Palumaa, P.; Žerovnik, E. The Role of Initial Oligomers in Amyloid Fibril Formation by Human Stefin B. Int. J. Mol. Sci. 2013, 14, 18362-18384.

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