Chirality of amyloid suprastructures.
Amyloids are pathological fibrillar aggregates of proteins related to more than 20 different diseases. Amyloid fibers have a characteristic cross-beta structure consisting of a series of beta-strands extended perpendicular to the fiber axis and joined by hydrogen bonds parallel to the fiber direction. Fibril aggregation results in helical suprastructures. Here we used high-resolution SEM and cryo-SEM for the study of chirality in the amyloid suprastructure. We found that amyloids of Abeta1-40 and hen lysozyme form at all hierarchical levels always and only left-handed helices. In contrast, amyloid fibers formed by the N-terminal sequence of serum amyloid A (SAA1-12) consist of right-handed helices exclusively. Consistently, the peptide enantiomer, formed of (R)-aminoacids, aggregates exclusively in left-handed helices. We conclude that the opposite handedness of the SAA1-12 amyloids is an intrinsic feature of the peptide structure. The left-handed chirality observed for the Abeta1-40 and hen lysozyme amyloid suprastructures is consistent with the conventional beta-sheet structural model. In contrast, the right-handedness observed in (all-S) SAA1-12 fibers indicates that the cross-beta structure of SAA1-12 fibers is probably not formed of beta-sheets. Whatever the answer to the dilemma of the right-handed helicity of SAA1-12 amyloid fibers is, its existence shows that the supramolecular chirality of amyloid fibers is not only dictated by the molecular chirality of the component molecules but also by their structural organization.
Rubin
Noa
N
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel 76100.
Perugia
Emanuel
E
Goldschmidt
Michal
M
Fridkin
Mati
M
Addadi
Lia
L
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D006801:Humans; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009113:Muramidase / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D000685:Serum Amyloid A Protein / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D000685:Serum Amyloid A Protein; C078592:amyloid beta-protein (1-40); D009113:Muramidase