学術雑誌論文

学術雑誌論文

text

Journal of Biological Chemistry. 2003, 278(47), p. 47016-47024

Amyloid Fibril Formation in the Context of Full-length Protein : EFFECTS OF PROLINE MUTATIONS ON THE AMYLOID FIBRIL FORMATION OF β2-MICROGLOBULIN

American Society for Biochemistry and Molecular Biology

英語

text

2003-11

https://doi.org/10.1074/jbc.M304473200

This research was originally published in the Journal of Biological Chemistry. Takeshi Chiba, Yoshihisa Hagihara, Takashi Higurashi, Kazuhiro Hasegawa, Hironobu Naiki and Yuji Goto. Amyloid Fibril Formation in the Context of Full-length Protein: EFFECTS OF PROLINE MUTATIONS ON THE AMYLOID FIBRIL FORMATION OF β2-MICROGLOBULIN. J. Biol. Chem. 2003; 278, 47016-47024. © the American Society for Biochemistry and Molecular Biology

β2-Microglobulin (β2-m), a typical immunoglobulin domain made of seven β-strands, is a major component of amyloid fibrils formed in dialysis-related amyloidosis. To understand the mechanism of amyloid fibril formation in the context of full-length protein, we prepared various mutants in which proline (Pro) was introduced to each of the seven β-strands of β2-m. The mutations affected the amyloidogenic potential of β2-m to various degrees. In particular, the L23P, H51P, and V82P mutations significantly retarded fibril extension at pH 2.5. Among these, only L23P is included in the known “minimal” peptide sequence, which can form amyloid fibrils when isolated as a short peptide. This indicates that the residues in regions other than the minimal sequence, such as H51P and V82P, determine the amyloidogenic potential in the full-length protein. To further clarify the mutational effects, we measured their stability against guanidine hydrochloride of the native state at pH 8.0 and the amyloid fibrils at pH 2.5. The amyloidogenicity of mutants showed a significant correlation with the stability of the amyloid fibrils, and little correlation was observed with that of the native state. It has been proposed that the stability of the native state and the unfolding rate to the amyloidogenic precursor as well as the conformational preference of the denatured state determine the amyloidogenicity of the proteins. The present results reveal that, in addition, stability of the amyloid fibrils is a key factor determining the amyloidogenic potential of the proteins.

71299

Amyloid Fibril Formation in the Context of Full-length Protein : EFFECTS OF PROLINE MUTATIONS ON THE AMYLOID FIBRIL FORMATION OF β2-MICROGLOBULIN

American Society for Biochemistry and Molecular Biology

英語

2003-11

Journal of Biological Chemistry

278

47

47016

47024

https://doi.org/10.1074/jbc.M304473200

https://hdl.handle.net/11094/71299