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Sulskis, Darius
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Iashchishyn, I. A., Sulskis, D., Ngoc, M. N., Smirnovas, V. & Morozova-Roche, L. A. (2017). Finke-Watzky Two-Step Nucleation-Autocatalysis Model of S100A9 Amyloid Formation: Protein Misfolding as "Nucleation" Event [Letter to the editor]. ACS Chemical Neuroscience, 8(10), 2152-2158
Open this publication in new window or tab >>Finke-Watzky Two-Step Nucleation-Autocatalysis Model of S100A9 Amyloid Formation: Protein Misfolding as "Nucleation" Event
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2017 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 8, no 10, p. 2152-2158Article in journal, Letter (Refereed) Published
Abstract [en]

Quantitative kinetic analysis is critical for understanding amyloid mechanisms. Here we demonstrate the application of generic Finke-Watzky (F-W) two-step nucleation-autocatalytic growth model to the concentration-dependent amyloid kinetics of proinflammatory alpha-helical S100A9 protein at pH 7.4 and at 37 and 42 degrees C. The model is based on two pseudoelementary reaction steps applied without further analytical constraints, and its treatment of S100A9 amyloid self-assembly demonstrates that initial misfolding and beta-sheet formation, defined as "nucleation" step, spontaneously takes place within individual S100A9 molecules at higher rate than the subsequent fibrillar growth. The latter, described as an autocatalytic process, will proceed if misfolded amyloid-prone S100A9 is populated on a macroscopic time scale. Short lengths of S100A9 fibrils are consistent with the F-W model. The analysis of fibrillar length distribution by the Beker-Doring model demonstrates independently that such distribution is solely determined by slow fibril growth and there is no fragmentation or secondary pathways decreasing fibrillar length.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
Keywords
Amyloid, autocatalysis, Finke-Watzky model, growth, kinetics, nucleation, S100A9
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Neurosciences
Identifiers
urn:nbn:se:umu:diva-141827 (URN)10.1021/acschemneuro.7b00251 (DOI)000413502700010 ()28759719 (PubMedID)
Available from: 2017-11-27 Created: 2017-11-27 Last updated: 2018-06-09Bibliographically approved
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