Globular Tetramers of beta(2)-Microglobulin assemble into elaborate amyloid fibrils
White, Helen E. and Hodgkinson, J.L. and Jahn, T.R. and Cohen-Krausz, Sara and Gosal, W.S. and Muller, S. and Orlova, Elena and Radford, S.E. and Saibil, Helen (2009) Globular Tetramers of beta(2)-Microglobulin assemble into elaborate amyloid fibrils. Journal of Molecular Biology 389 (1), pp. 48-57. ISSN 0022-2836.
Amyloid fibrils are ordered polymers in which constituent polypeptides adopt a non-native fold. Despite their importance in degenerative human diseases, the overall structure of amyloid fibrils remains unknown. High-resolution studies of model peptide assemblies have identified residues forming cross-β-strands and have revealed some details of local β-strand packing. However, little is known about the assembly contacts that define the fibril architecture. Here we present a set of three-dimensional structures of amyloid fibrils formed from full-length β2-microglobulin, a 99-residue protein involved in clinical amyloidosis. Our cryo-electron microscopy maps reveal a hierarchical fibril structure built from tetrameric units of globular density, with at least three different subunit interfaces in this homopolymeric assembly. These findings suggest a more complex superstructure for amyloid than hitherto suspected and prompt a re-evaluation of the defining features of the amyloid fold.
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Research Centre:||Structural Molecular Biology, Institute of (ISMB)|
|Date Deposited:||04 Aug 2010 14:09|
|Last Modified:||06 Dec 2016 11:14|
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