Poster Presentation The 45th Lorne Conference on Protein Structure and Function 2020

Insights into molecular mechanisms of self-assembly of amyloids in presence and absence of metals (#224)

Yifat Miller 1
  1. Ben-Gurion University of the Negev, Beer-Sheva, ISRAEL, Israel

The pathological self-assembly (or aggregation) of amyloid proteins into toxic aggregate species plays important role in the amyloidogenic diseases. The first part of the lecture will focus on three of the most prevalent of these diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD) and type 2 diabetes (T2D). The particular amyloids that have been implicated in the development of these three diseases are amyloid β (Aβ) in AD, α-synuclein (AS) in PD and amylin and insulin in T2D. Metal ions are factors that affect the self-assembly of amyloids in many amyloid diseases. Computational studies may help to elucidate the various conformations of metal-full-length amyloid fibrils.1 The mechanisms through which amylin peptides are self-assembled with absence and with presence of metal ions will be presented. There are various pathways in which amylin can self-assemble into fibrils,2,3 but metal ions decrease the number of pathways of self-assembly.4,5 Contrarily, in Aβ, the metal ions increase the polymorphism of amyloid fibrils, and yield to many pathways.6 Finally, the effect of metals on AS fibrillation increases the possible pathway mechanisms and demonstrates disruptions of the fibrils.7,8

 

References

  1. Wineman-Fisher, V. et al. Chem. Rev. 2016, 327, 20-26.
  2. Wineman-Fisher, V. et al. 2015, 16, 156-165.
  3. Wineman-Fisher, V., Miller, Y. PCCP 2016, 18, 12438-42.
  4. Wineman-Fisher, V. Miller, Y. ACS Chem. Neuro. 2017, 8, 2078-2087.
  5. Wineman-Fisher, V., Miller, Y. PCCP 2016, 18, 21590-99.
  6. Miller, Y., et al. PNAS 2010, 107, 9490-95.
  7. Miller, Y. et al. Chem. Rev. 2012, 256, 2245-52.
  8. Bloch, D.N et al. Inorg. Chem. 2019, DOI: 10.1021/acs.inorgchem.9b01337.