465612 Varying Effects of Kosmotropic and Chaotropic Anions on Amyloid beta1-42 Aggregation Kinetics and Fibril Formation

Friday, November 18, 2016: 2:00 PM
Continental 9 (Hilton San Francisco Union Square)
Aditi Sharma1, Sven H. Behrens1, Yury O. Chernoff2 and Andreas S. Bommarius3, (1)School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, (2)Biology, Georgia Institute of Technology, Atlanta, GA, (3)School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA

Aggregation of amyloid-β peptides to form plaques is considered to trigger the pathogenesis of Alzheimer’s disease (AD). A𝛽1-42, which is the most toxic amyloid-β peptide, has been widely studied to understand its aggregation properties and role in the pathogenesis of AD. However, the effect of ions on aggregation of A𝛽1-42 has not been investigated systematically. In this work we have studied the effect of ions of the Hofmeister series on the aggregation of A𝛽1-42. Previous work from our group had demonstrated that Sup35NM protein containing the prion domain of yeast prion protein Sup35p exhibited faster aggregation in the presence of strongly hydrated anions (kosmotropes), and slower aggregation in the presence of poorly hydrated anions (chaotropes)1,2. The Hofmeister salts also determined the amyloid strain that was preferentially formed, and affected the specificity of species barrier of the Sup35 protein between three closely related Saccharomyces species3. In this work, we have investigated how Hofmeister ions affect the aggregation kinetics of A𝛽1-42 peptide. Our experiments show that while the relative effects of kosmotropic and chaotropic ions on aggregation kinetics are similar, the absolute effects of the chaotropic salts on the aggregation of A𝛽1-42 peptide are different from Sup35NM. Further, the differences in the amyloid strains formed by A𝛽1-42 in the presence of Hofmeister salts have also been studied by microscopy and electrophoresis techniques to gain better insights into the aggregation mechanism of A𝛽1-42.

[1] Rubin, J., Khosravi, H., Bruce, K. L., Lydon, M. E., Behrens, S. H., Chernoff, Y. O. and Bommarius, A. S., 2013. Ion-specific effects on prion nucleation and strain formation. Journal of Biological Chemistry, 288(42), pp.30300-30308. doi: 10.1074/jbc.M113.467829

[2] Yeh, V., Broering, J. M., Romanyuk, A., Chen, B., Chernoff, Y. O. and Bommarius, A. S. (2010), The Hofmeister effect on amyloid formation using yeast prion protein. Protein Science, 19: 47–56. doi: 10.1002/pro.281

[3] Sharma, A., Bruce, K. L., Chen, B., Gyoneva, S., Behrens, S. H., Bommarius, A. S. and Chernoff, Y. O., 2016. Contributions of the Prion Protein Sequence, Strain, and Environment to the Species Barrier. Journal of Biological Chemistry, 291(3), pp.1277-1288. doi: 10.1074/jbc.M115.684100


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See more of this Session: Protein Structure, Function, and Stability
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