Back to Journals » International Journal of Nanomedicine » Volume 10 » Issue 1

Amyloids in solid-state nuclear magnetic resonance: potential causes of the usually low resolution

Authors Espargaró A, Busquets MA, Estelrich J, Sabate R

Received 27 May 2015

Accepted for publication 18 July 2015

Published 9 November 2015 Volume 2015:10(1) Pages 6975—6983

DOI https://doi.org/10.2147/IJN.S89385

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J Webster


Alba Espargaró, Maria Antònia Busquets, Joan Estelrich, Raimon Sabate

Department of Physical Chemistry, School of Pharmacy, Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain

Abstract: Amyloids are non-crystalline and insoluble, which imply that the classical structural biology tools, ie, X-ray crystallography and solution nuclear magnetic resonance (NMR), are not suitable for their analysis. In the last years, solid-state NMR (ssNMR) has emerged as an alternative tool to decrypt the structural signatures of amyloid fibrils, providing major contributions to our understanding of molecular structures of amyloids such as β-amyloid peptide associated with Alzheimer’s disease or fungal prions, among others. Despite this, the wide majority of amyloid fibrils display low resolution by ssNMR. Usually, this low resolution has been attributed to a high disorder or polymorphism of the fibrils, suggesting the existence of diverse elementary β-sheet structures. Here, we propose that a single β-sheet structure could be responsible for the broadening of the line widths in the ssNMR spectra. Although the fibrils and fibers consist of a single elementary structure, the angle of twist of each individual fibril in the mature fiber depends on the number of individual fibrils as well as the fibril arrangement in the final mature fiber. Thus, a wide range of angles of twist could be observed in the same amyloid sample. These twist variations involve changes in amino acid alignments that could be enough to limit the ssNMR resolution.

Keywords: amyloid, fibril, misfolding, β-structure, ssNMR, NMR, β-sheet

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]