Adsorption free energy predicts amyloid protein nucleation rates

Toprakcioglu Z, Kamada A, Michaels TCT, Xie M, Krausser J, Wei J, Šarić A, Vendruscolo M, Knowles TPJ. 2022. Adsorption free energy predicts amyloid protein nucleation rates. Proceedings of the National Academy of Sciences of the United States of America. 119(31), e2109718119.

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Author
Toprakcioglu, Zenon; Kamada, Ayaka; Michaels, Thomas C.T.; Xie, Mengqi; Krausser, Johannes; Wei, Jiapeng; Šarić, AnđelaISTA ; Vendruscolo, Michele; Knowles, Tuomas P.J.
Department
Abstract
Primary nucleation is the fundamental event that initiates the conversion of proteins from their normal physiological forms into pathological amyloid aggregates associated with the onset and development of disorders including systemic amyloidosis, as well as the neurodegenerative conditions Alzheimer’s and Parkinson’s diseases. It has become apparent that the presence of surfaces can dramatically modulate nucleation. However, the underlying physicochemical parameters governing this process have been challenging to elucidate, with interfaces in some cases having been found to accelerate aggregation, while in others they can inhibit the kinetics of this process. Here we show through kinetic analysis that for three different fibril-forming proteins, interfaces affect the aggregation reaction mainly through modulating the primary nucleation step. Moreover, we show through direct measurements of the Gibbs free energy of adsorption, combined with theory and coarse-grained computer simulations, that overall nucleation rates are suppressed at high and at low surface interaction strengths but significantly enhanced at intermediate strengths, and we verify these regimes experimentally. Taken together, these results provide a quantitative description of the fundamental process which triggers amyloid formation and shed light on the key factors that control this process.
Publishing Year
Date Published
2022-07-28
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Acknowledgement
The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt (agreement 337969). We are grateful for financial support from the Biotechnology and Biological Sciences Research Council (BBSRC) (T.P.J.K.), the Newman Foundation (T.P.J.K.), the Wellcome Trust (T.P.J.K. and M.V.), Peterhouse College Cambridge (T.C.T.M.), the ERC Starting Grant (StG) Non-Equilibrium Protein Assembly (NEPA) (A.S.), the Royal Society (A.S.), the Academy of Medical Sciences (A.S. and J.K.), and the Cambridge Centre for Misfolding Diseases (CMD).
Volume
119
Issue
31
Article Number
e2109718119
ISSN
eISSN
IST-REx-ID

Cite this

Toprakcioglu Z, Kamada A, Michaels TCT, et al. Adsorption free energy predicts amyloid protein nucleation rates. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(31). doi:10.1073/pnas.2109718119
Toprakcioglu, Z., Kamada, A., Michaels, T. C. T., Xie, M., Krausser, J., Wei, J., … Knowles, T. P. J. (2022). Adsorption free energy predicts amyloid protein nucleation rates. Proceedings of the National Academy of Sciences of the United States of America. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2109718119
Toprakcioglu, Zenon, Ayaka Kamada, Thomas C.T. Michaels, Mengqi Xie, Johannes Krausser, Jiapeng Wei, Anđela Šarić, Michele Vendruscolo, and Tuomas P.J. Knowles. “Adsorption Free Energy Predicts Amyloid Protein Nucleation Rates.” Proceedings of the National Academy of Sciences of the United States of America. Proceedings of the National Academy of Sciences, 2022. https://doi.org/10.1073/pnas.2109718119.
Z. Toprakcioglu et al., “Adsorption free energy predicts amyloid protein nucleation rates,” Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 31. Proceedings of the National Academy of Sciences, 2022.
Toprakcioglu Z, Kamada A, Michaels TCT, Xie M, Krausser J, Wei J, Šarić A, Vendruscolo M, Knowles TPJ. 2022. Adsorption free energy predicts amyloid protein nucleation rates. Proceedings of the National Academy of Sciences of the United States of America. 119(31), e2109718119.
Toprakcioglu, Zenon, et al. “Adsorption Free Energy Predicts Amyloid Protein Nucleation Rates.” Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 31, e2109718119, Proceedings of the National Academy of Sciences, 2022, doi:10.1073/pnas.2109718119.
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2023-10-04
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