Details

Autor(en) / Beteiligte

• White, HE
• Hodgkinson, J L
• Jahn, T R
• Cohen-Krausz, S
• Gosal, W S
• Muller, S
• Orlova, E V
• Radford, SE
• Saibil, H R

Titel

Globular Tetramers of beta sub(2)-Microglobulin Assemble into Elaborate Amyloid Fibrils

Ist Teil von

• Journal of molecular biology, 2009-05, Vol.389 (1), p.48-57

Erscheinungsjahr

2009

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 sub(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.