Electron paramagnetic resonance spectroscopy measures the distance between the external β-strands of folded α-synuclein in amyloid fibrils.

A Relationship between the Transient Structure in the Monomeric State and the Aggregation Propensities of α-Synuclein and β-Synuclein

α-Synuclein is an intrinsically disordered protein whose aggregation is implicated in Parkinson's disease. A second member of the synuclein family, β-synuclein, shares significant sequence similarity with α-synuclein but is much more resistant to aggregation. β-Synuclein is missing an 11-residue stretch in the central non-β-amyloid component region that forms the core of α-synuclein amyloid fib...

Long-Range Distances in Amyloid Fibrils of α-Synuclein from PELDOR Spectroscopy**

a-Synuclein (aS), a small protein containing 140 amino acids, undergoes self-assembly into amyloid fibrils and plaques (Lewy bodies), which are pathological hallmarks of Parkinson s disease (PD) as well as other neurodegenerative diseases. While oligomeric species of aS are considered to exert the neurotoxic activity that can be rescued by reducing those oligomers either by diversion to smaller...

Structural origin of polymorphism of Alzheimer's amyloid β-fibrils.

Formation of senile plaques containing amyloid fibrils of Aβ (amyloid β-peptide) is a pathological hallmark of Alzheimer's disease. Unlike globular proteins, which fold into unique structures, the fibrils of Aβ and other amyloid proteins often contain multiple polymorphs. Polymorphism of amyloid fibrils leads to different toxicity in amyloid diseases and may be the basis for prion strains, but ...

Conserved core of amyloid fibrils of wild type and A30P mutant α-synuclein.

The major component of neural inclusions that are the pathological hallmark of Parkinson's disease are amyloid fibrils of the protein α-synuclein (aS). Here we investigated if the disease-related mutation A30P not only modulates the kinetics of aS aggregation, but also alters the structure of amyloid fibrils. To this end we optimized the method of quenched hydrogen/deuterium exchange coupled to...

Long-Range Distances in Amyloid Fibrils of a-Synuclein from PELDOR Spectroscopy**