Amyloid Fibril Polymorphism: Almost Identical on the Atomic Level, Mesoscopically Very Different.
Carolin Seuring1, Joeri Verasdonck1, Philippe Ringler2
1Laboratory of Physical Chemistry, ETH Zürich , Vladimir-Prelog-Weg 2, 8093 Zürich, Switzerland.
The Journal of Physical Chemistry. B
|January 12, 2017
Summary
Salt conditions influence amyloid fibril structure. While monomer structures are similar, electrostatic repulsions lead to distinct flat or twisted β-endorphin fibril morphologies at the mesoscopic scale.
Area of Science:
- Biochemistry
- Biophysics
- Structural Biology
Background:
- Amyloid fibrils are protein aggregates implicated in various diseases.
- β-endorphin can form amyloid fibrils with different morphologies.
- Salt concentration is known to affect polymer assembly and morphology.
Purpose of the Study:
- To investigate the structural basis of amyloid polymorphism in β-endorphin fibrils.
- To compare the atomic-level structures of salt-induced flat and salt-free twisted β-endorphin fibrils.
- To elucidate the role of electrostatic interactions in fibril morphology.
Main Methods:
- Negative-stain transmission electron microscopy (TEM)
- Scanning transmission electron microscopy (STEM)
- 3D solid-state nuclear magnetic resonance (NMR) spectroscopy
Main Results:
- Fibrils assembled in salt formed flat, striated ribbons.
- Fibrils assembled without salt formed mainly twisted filaments.
- 3D solid-state NMR revealed highly similar chemical shifts (13C and 15N) for both fibril types.
- Atomic-level monomer structures and molecular interfaces are nearly identical between flat and twisted fibrils.
Conclusions:
- Small structural differences at the atomic level propagate to create distinct mesoscopic fibril morphologies (flat vs. twisted).
- Electrostatic intermolecular repulsions, influenced by salt conditions, are the primary drivers of the observed mesoscopic structural polymorphism.
- This study provides insights into the principles governing amyloid assembly and polymorphism.
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