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

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

Acknowledgments

RS is beneficiary of a contract under the Ramón y Cajal programme (RYC-2011-07987), and AE is beneficiary of a contract under the Juan de la Cierva programme (JCI-2012-12193), both financed by the Spanish Ministerio de Economía y Competitividad (MINECO). MAB and JE thank the financial support given by the MINECO to the project MAT2012-36270-C04-03. The authors thank the projects 2014SGR227 and 2014SGR938 of the Generalitat of Catalunya.

Disclosure

The authors report no conflicts of interest in this work.