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The Effect of Osmolytes on Protein Fibrillation
iNANO, Center for Insoluble Protein Structures (inSPIN), Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark
Hochschule Biberach, Pharmaceutical Biotechnology, Hubertus-Liebrecht-Str. 35, D-88400 Biberach, Germany
Present address: Zealand Pharma A/S, Smedeland 36, 2600 Glostrup, Denmark.
* Author to whom correspondence should be addressed.
Received: 9 February 2012; in revised form: 10 March 2012 / Accepted: 13 March 2012 / Published: 21 March 2012
Abstract: Osmolytes are small molecules that are exploited by cells as a protective system against stress conditions. They favour compact protein states which makes them stabilize globular proteins in vitro and promote folding. Conversely, this preference for compact states promotes aggregation of unstructured proteins. Here we combine a brief review of the effect of osmolytes on protein fibrillation with a report of the effect of osmolytes on the unstructured peptide hormone glucagon. Our results show that osmolytes either accelerate the fibrillation kinetics or leave them unaffected, with the exception of the osmolyte taurine. Furthermore, the osmolytes that affected the shape of the fibrillation time profile led to fibrils with different structure as revealed by CD. The structural changes induced by Pro, Ser and choline-O-sulfate could be due to specific osmolytes binding to the peptides, stabilizing an otherwise labile fibrillation intermediate.
Keywords: glucagon; amyloid; taurine; polymorphism; fibrillation mechanism
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MDPI and ACS Style
Macchi, F.; Eisenkolb, M.; Kiefer, H.; Otzen, D.E. The Effect of Osmolytes on Protein Fibrillation. Int. J. Mol. Sci. 2012, 13, 3801-3819.
Macchi F, Eisenkolb M, Kiefer H, Otzen DE. The Effect of Osmolytes on Protein Fibrillation. International Journal of Molecular Sciences. 2012; 13(3):3801-3819.
Macchi, Francesca; Eisenkolb, Maike; Kiefer, Hans; Otzen, Daniel E. 2012. "The Effect of Osmolytes on Protein Fibrillation." Int. J. Mol. Sci. 13, no. 3: 3801-3819.