Comparison of Alzheimer Abeta(1-40) and Abeta(1-42) amyloid fibrils reveals similar protofilament structures.
We performed mass-per-length (MPL) measurements and electron cryomicroscopy (cryo-EM) with 3D reconstruction on an Abeta(1-42) amyloid fibril morphology formed under physiological pH conditions. The data show that the examined Abeta(1-42) fibril morphology has only one protofilament, although two protofilaments were observed with a previously studied Abeta(1-40) fibril. The latter fibril was resolved at 8 A resolution showing pairs of beta-sheets at the cores of the two protofilaments making up a fibril. Detailed comparison of the Abeta(1-42) and Abeta(1-40) fibril structures reveals that they share an axial twofold symmetry and a similar protofilament structure. Furthermore, the MPL data indicate that the protofilaments of the examined Abeta(1-40) and Abeta(1-42) fibrils have the same number of Abeta molecules per cross-beta repeat. Based on this data and the previously studied Abeta(1-40) fibril structure, we describe a model for the arrangement of peptides within the Abeta(1-42) fibril.
Rosenstiel Basic Medical Sciences Research Center and Howard Hughes Medical Institute, Brandeis University, MS 029, Waltham, MA 02454-9110, USA.
Matthias
M
Schmidt
Carsten
C
Sachse
Walter
W
Richter
Chen
C
Xu
Marcus
M
Fändrich
Nikolaus
N
Grigorieff
D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000737:chemistry / Q000648:ultrastructure*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D020285:Cryoelectron Microscopy; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)