Neurotoxic Oligomer’s Structure Uncovered | February 14, 2011 Issue - Vol. 89 Issue 7 | Chemical & Engineering News
Volume 89 Issue 7 | p. 35 | Concentrates
Issue Date: February 14, 2011

Neurotoxic Oligomer’s Structure Uncovered

Small-angle X-ray scattering enabled researchers to analyze aggregated α-synuclein associated with Parkinson’s disease
Department: Science & Technology
Keywords: Parkinson’s disease, α-synuclein, fibrillation, neurotoxic oligomers
Twisty Stack
A SAXS-derived structure of a wreathlike α-synuclein oligomer (top) and a proposed model of a fibril (bottom) created by stacking and then twisting the oligomers like coins.
Credit: Proc. Natl. Acad. Sci. USA
8907scic5_live-1
 
Twisty Stack
A SAXS-derived structure of a wreathlike α-synuclein oligomer (top) and a proposed model of a fibril (bottom) created by stacking and then twisting the oligomers like coins.
Credit: Proc. Natl. Acad. Sci. USA

Using small-angle X-ray scattering (SAXS), an international research team has determined the low-resolution structure of α-synuclein oligomer, an aggregated protein intermediate thought to be part of the fibril formation process that is a hallmark of Parkinson’s disease (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1013225108). Scientists have suggested that oligomers, rather than protein monomers or fibrils, are the toxic species involved in the neurodegenerative disorder. But questions about the role of oligomers in fibril formation remain. Because SAXS can be applied in situ to a multicomponent solution, the researchers, led by Daniel E. Otzen of Denmark’s University of Aarhus and Bente Vestergaard of the University of Copenhagen, were able to probe the oligomers during fibrillation. Through ab initio modeling of the data, they found that α-synuclein oligomers are each composed of 16 monomers on average and have a wreathlike shape with dimensions of 180 × 90 Å. This shape and size suggest that an oligomer’s toxicity lies in its ability to perforate cell membranes, the researchers say, and that the toxic species are an integral part of fibril formation, stacking like coins to build the bundled filaments./p>

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

Leave A Comment

*Required to comment