White Rose University Consortium logo
University of Leeds logo University of Sheffield logo York University logo

A common beta-sheet architecture underlies in vitro and in vivo beta(2)-microglobulin amyloid fibrils

Jahn, T.R., Tennent, G.A. and Radford, S.E. (2008) A common beta-sheet architecture underlies in vitro and in vivo beta(2)-microglobulin amyloid fibrils. Journal of Biological Chemistry, 283 (25). pp. 17279-17286. ISSN 1083-351X

Available under licence : See the attached licence file.

Download (551Kb)


Misfolding and aggregation of normally soluble proteins into amyloid fibrils and their deposition and accumulation underlies a variety of clinically significant diseases. Fibrillar aggregates with amyloid-like properties can also be generated in vitro from pure proteins and peptides, including those not known to be associated with amyloidosis. Whereas biophysical studies of amyloid-like fibrils formed in vitro have provided important insights into the molecular mechanisms of amyloid generation and the structural properties of the fibrils formed, amyloidogenic proteins are typically exposed to mild or more extreme denaturing conditions to induce rapid fibril formation in vitro. Whether the structure of the resulting assemblies is representative of their natural in vivo counterparts, thus, remains a fundamental unresolved issue. Here we show using Fourier transform infrared spectroscopy that amyloid-like fibrils formed in vitro from natively folded or unfolded β2-microglobulin (the protein associated with dialysis-related amyloidosis) adopt an identical β-sheet architecture. The same β-strand signature is observed whether fibril formation in vitro occurs spontaneously or from seeded reactions. Comparison of these spectra with those of amyloid fibrils extracted from patients with dialysis-related amyloidosis revealed an identical amide I' absorbance maximum, suggestive of a characteristic and conserved amyloid fold. Our results endorse the relevance of biophysical studies for the investigation of the molecular mechanisms of β2-microglobulin fibrillogenesis, knowledge about which may inform understanding of the pathobiology of this protein.

Item Type: Article
Copyright, Publisher and Additional Information: © 2008 American Society for Biochemistry and Molecular Biology. This is an author produced version of a paper published in Journal of Biological Chemistry. Uploaded in accordance with the publisher's self archiving policy.
Institution: The University of Leeds
Academic Units: The University of Leeds > University of Leeds Research Centres and Institutes > Astbury Centre for Structural Molecular Biology (Leeds)
Depositing User: Sherpa Assistant
Date Deposited: 25 Jul 2008 11:28
Last Modified: 08 Feb 2013 17:05
Published Version: http://dx.doi.org/10.1074/jbc.M710351200
Status: Published
Publisher: American Society for Biochemistry and Molecular Biology
Identification Number: 10.1074/jbc.M710351200
URI: http://eprints.whiterose.ac.uk/id/eprint/4085

Actions (repository staff only: login required)