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Martina Huber (LION) and fellow researchers are "on the way to understanding amyloid fibrils" (article in Applied Magnetic Resonance)

[27-01-2015]

In amyloid fibrils, proteins assemble into nanometer-sized columns that have the flexibility of steel. The glue that converts the spaghetti-like proteins to assemble into self-repeating structures that form the fibril are normal interprotein interaction forces, so the magic lies in the precise arrangement of the protein. The Electron Paramagnetic Resonance group of Martina Huber in Leiden, together with the Twente/AMOLF group of Vinod Subramaniam, installed nano-sized markers, measured distances and found - based on gross approximations - a possible arrangement of the fibril for Parkinson's protein alpha-synuclein. They published their findings on peeking into the amyloid structure in the Applied Magnetic Resonance. 

Abstract

"Amyloid fibrils and plaques are the hallmark of neurodegenerative diseases. In Parkinson’s disease, plaques (Lewy bodies) consist predominantly of the a-synuclein (aS) protein. To understand aggregation, the molecular architecture of aS fibrils needs to be known. Here, we determine nm-distance constraints for the protein in the fibril by double electron–electron paramagnetic resonance (DEER) on doubly spin-labeled aS variants, diamagnetically diluted with wild-type aS to suppress intermolecular interactions. Intramolecular distances in three pairs (56/69, 56/90 and 69/90) are reported. An approach to derive a model for the fibril fold from sparse distance data assuming only parallel b-sheets is described. Using the distances obtained in this study as input, a model is obtained with three strands, comprising residues 56–90, in which the strands consist of 8–12 residues each. Limitations of the approach are discussed in detail, showing that the interpretation  of the data does not yet yield an unambiguous structure model. Possible avenues to improve this situation are described."

For the full article, download the file below. For more information on Martina Huber's research, please visit her group website.

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