RESEARCH ARTICLE


Insights into the Structure of Amyloid Fibrils



Karen E. Marshall, Louise C. Serpell*
Department of Biochemistry, John Maynard Smith Building, School of Life Sciences, University of Sussex, Falmer, East Sussex, BN1 9QG, UK

Article Information


Identifiers and Pagination:

Year: 2009
Volume: 2
First Page: 185
Last Page: 192
Publisher Id: TOBIOJ-2-185
DOI: 10.2174/1874196700902010185

Article History:

Received Date: 21/04/2009
Revision Received Date: 07/07/2009
Acceptance Date: 09/07/2009
Electronic publication date: 31/12/2009
Collection year: 2009

© 2009 Marshall and Serpell

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Biochemistry, John Maynard Smith Building, School of Life Sciences, University of Sussex, Falmer, East Sussex, BN1 9QG, UK; Tel: +44 1273 877363; Fax: +44 1273 678433; E-mail: L.C.Serpell@sussex.ac.uk


Abstract

Various proteins and peptides are able to self assemble into amyloid fibrils that are associated with disease. Structural characterisation of these fibres is limited by their insoluble and heterogeneous nature. However, advances in various techniques including X-ray diffraction, cryo-electron microscopy and solid state NMR have provided detailed information on various amyloid fibrils, from the long range order and macromolecular structure to the atomic interactions that promote assembly and stabilise the amyloid core. The cross-β model has been widely accepted as a generic structure for most amyloid fibrils and is discussed in detail. It is clear, however, that polymorphisms are present, even in fibrils formed from the same precursor protein, and that these may represent differences in packing at a molecular level. To fully understand the roles of particular residues in amyloid formation and structure, short peptides can be used in conjunction with mutagenesis studies to assess their effects. The structural insights gained using a combination of techniques to study both full-length, disease related peptides and short fragments are essential if progress is to be made towards understanding why these fibres form and how to prevent their formation.

Keywords: Amyloid, structure, X-ray fibre diffraction, Solid State NMR, cross-β.