Stereospecific amyloid-like fibril formation by a peptide fragment of β2-microglobulin

Hiromasa Wadai, Kei Ichi Yamaguchi, Satoshi Takahashi, Takashi Kanno, Tomoji Kawai, Hironobu Naiki, Yuji Goto

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

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 extended by monomers. The results revealed that only the homologous extensions proceed smoothly, i.e., the growth of L-seeds by L-monomers or D-seeds by D-monomers. The results suggest that, while the fibrils derived from L- and D-peptides form in a similar manner but with opposite stereochemistry, a cross-reaction between them is prevented because the geometry of the mixed sheet cannot satisfy dominant factors for β-sheet stabilization.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalBiochemistry
Volume44
Issue number1
DOIs
Publication statusPublished - 2005 Jan 11
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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