Globular tetramers of beta(2)-microglobulin assemble into elaborate amyloid fibrils.
J Mol Biol
; 389(1): 48-57, 2009 May 29.
Article
em En
| MEDLINE
| ID: mdl-19345691
ABSTRACT
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-beta-strands and have revealed some details of local beta-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 beta(2)-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Microglobulina beta-2
/
Amiloide
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article