学術雑誌論文

学術雑誌論文

text

Journal of Biological Chemistry. 2004, 279(11), p. 10814-10821

Optimum Amyloid Fibril Formation of a Peptide Fragment Suggests the Amyloidogenic Preference of β2-Microglobulin under Physiological Conditions

American Society for Biochemistry and Molecular Biology

英語

text

2004-03

https://doi.org/10.1074/jbc.M310334200

This research was originally published in the Journal of Biological Chemistry. Yumiko Ohhashi, Kazuhiro Hasegawa, Hironobu Naiki and Yuji Goto. Optimum Amyloid Fibril Formation of a Peptide Fragment Suggests the Amyloidogenic Preference of β2-Microglobulin under Physiological Conditions. J. Biol. Chem. 2004; 279, 10814-10821. © the American Society for Biochemistry and Molecular Biology

β2-Microglobulin (β2m) is a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Although full-length β2m readily forms amyloid fibrils in vitro by seed-dependent extension with a maximum at pH 2.5, fibril formation under physiological conditions as detected in patients has been difficult to reproduce. A 22-residue K3 peptide of β2m, Ser20–Lys41, obtained by digestion with Acromobacter protease I, forms amyloid fibrils without seeding. To obtain further insight into the mechanism of fibril formation, we studied the pH dependence of fibril formation of the K3 peptide and its morphology using a ThT fluorescence assay and electron microscopy, respectively. K3 peptide formed amyloid fibrils over a wide range of pH values with an optimum around pH 7 and contrasted with the pH profile of the seed-dependent extension reaction of full-length β2m. This suggests that once the rigid native-fold of β2m is unfolded and additional factors triggering the nucleation process are provided, full-length β2m discloses an intrinsic potential to form amyloid fibrils at neutral pH. The fibril formation was strongly promoted by dimerization of K3 through Cys25. The morphology of the fibrils varied depending on the fibril formation conditions and the presence or absence of a disulfide bond. Various fibrils had the potential to seed fibril formation of full-length β2m accompanied with a characteristic lag phase, suggesting that the internal structures are similar.

71297

Optimum Amyloid Fibril Formation of a Peptide Fragment Suggests the Amyloidogenic Preference of β2-Microglobulin under Physiological Conditions

American Society for Biochemistry and Molecular Biology

英語

2004-03

Journal of Biological Chemistry

279

11

10814

10821

https://doi.org/10.1074/jbc.M310334200

https://hdl.handle.net/11094/71297