Stereospecific Amyloid-like Fibril Formation by a Peptide Fragment of β2-Microglobulin†

Understanding the role of the l/d-stereospecificity of amino acids is important in obtaining further insight into the mechanism of the formation of amyloid fibrils. β2-Microglobulin is a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. A 22-residue peptide of β2-microglobulin, Ser20−Lys41 (l-K3 peptide), obtained by digestion with Acromobacter protease I, formed amyloid-like fibrils in 50% (v/v) 2,2,2-trifluoroethanol and 10 mM HCl at 25 °C, as confirmed by thioflavin T fluorescence, circular dichroism spectra, and atomic force microscopy images. A synthetic K3 peptide composed of d-amino acids (d-K3 peptide) formed similar fibrils but with opposite chirality as indicated by circular dichroism spectra. A mixture of l-K3 and d-K3 peptides also formed fibrils, although the l- and d-amino acid composition of each fibril is unknown. To examine the possible cross-reactivity between l- and d-enantiomers, we carried out seeding experiments in which preformed seeds were ...