112477-20-0Relevant academic research and scientific papers
Chirality of amyloid suprastructures
Rubin, Noa,Perugia, Emanuel,Goldschmidt, Michal,Fridkin, Mati,Addadi, Lia
, p. 4602 - 4603 (2008)
Amyloids are pathological fibrillar aggregates of proteins related to more than 20 different diseases. Amyloid fibers have a characteristic cross-β structure consisting of a series of β-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 Aβ1-40 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 Aβ1-40 and hen lysozyme amyloid suprastructures is consistent with the conventional β-sheet structural model. In contrast, the right-handedness observed in (all-S) SAA1-12 fibers indicates that the cross-β structure of SAA1-12 fibers is probably not formed of β-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. Copyright
