scholarly journals Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Martin Nors Pedersen ◽  
Vito Foderà ◽  
Istvan Horvath ◽  
Andreas van Maarschalkerweerd ◽  
Katrine Nørgaard Toft ◽  
...  

Abstract Aggregation of proteins into amyloid deposits is the hallmark of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The suggestion that intermediate oligomeric species may be cytotoxic has led to intensified investigations of pre-fibrillar oligomers, which are complicated by their transient nature and low population. Here we investigate alpha-synuclein oligomers, enriched by a 2-pyridone molecule (FN075) and the conversion of oligomers into fibrils. As probed by leakage assays, the FN075 induced oligomers potently disrupt vesicles in vitro, suggesting a potential link to disease related degenerative activity. Fibrils formed in the presence and absence of FN075 are indistinguishable on microscopic and macroscopic levels. Using small angle X-ray scattering, we reveal that FN075 induced oligomers are similar, but not identical, to oligomers previously observed during alpha-synuclein fibrillation. Since the levels of FN075 induced oligomers correlate with the amounts of fibrils among different FN075:protein ratios, the oligomers appear to be on-pathway and modeling supports an ‘oligomer stacking model’ for alpha-synuclein fibril elongation.

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 39 ◽  
Author(s):  
Roman Kamyshinsky ◽  
Yury Chesnokov ◽  
Liubov Dadinova ◽  
Andrey Mozhaev ◽  
Ivan Orlov ◽  
...  

Rapid increase of intracellular synthesis of specific histone-like Dps protein that binds DNA to protect the genome against deleterious factors leads to in cellulo crystallization—one of the most curious processes in the area of life science at the moment. However, the actual structure of the Dps–DNA co-crystals remained uncertain in the details for more than two decades. Cryo-electron tomography and small-angle X-ray scattering revealed polymorphous modifications of the co-crystals depending on the buffer parameters. Two different types of the Dps–DNA co-crystals are formed in vitro: triclinic and cubic. Three-dimensional reconstruction revealed DNA and Dps molecules in cubic co-crystals, and the unit cell parameters of cubic lattice were determined consistently by both methods.


FEBS Letters ◽  
2019 ◽  
Vol 593 (12) ◽  
pp. 1360-1371 ◽  
Author(s):  
Liubov A. Dadinova ◽  
Yurii M. Chesnokov ◽  
Roman A. Kamyshinsky ◽  
Ivan A. Orlov ◽  
Maxim V. Petoukhov ◽  
...  

2015 ◽  
Vol 11 (1) ◽  
pp. 190-196 ◽  
Author(s):  
Cyril C. Curtain ◽  
Nigel M. Kirby ◽  
Haydyn D. T. Mertens ◽  
Kevin J. Barnham ◽  
Robert B. Knott ◽  
...  

Size exclusion chromatography with small angle X-ray scattering and ensemble optimisation modelling reveals conformers in random pool of α-synuclein.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Katsuya Araki ◽  
Naoto Yagi ◽  
Rie Nakatani ◽  
Hiroshi Sekiguchi ◽  
Masatomo So ◽  
...  

2007 ◽  
Vol 24 (10) ◽  
pp. 1844-1853 ◽  
Author(s):  
Dimitrios G. Fatouros ◽  
G. Roshan Deen ◽  
Lise Arleth ◽  
Bjorn Bergenstahl ◽  
Flemming Seier Nielsen ◽  
...  

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