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

Chiba, Takeshi; Hagihara, Yoshihisa; Higurashi, Takashi; Hasegawa, Kazuhiro; Naiki, Hironobu; Goto, Yuji

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

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

Chiba, Takeshi; Hagihara, Yoshihisa; Higurashi, Takashi et al.

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

Number of Access:489（2025-08-30 11:33 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/71299

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Title	Amyloid Fibril Formation in the Context of Full-length Protein : EFFECTS OF PROLINE MUTATIONS ON THE AMYLOID FIBRIL FORMATION OF β2-MICROGLOBULIN
Creator	CreatorName Chiba, Takeshi
	NRID 1000050357761 1000050357761 CreatorName Hagihara, Yoshihisa
	CreatorName Higurashi, Takashi
	NRID 1000060324159 1000060324159 CreatorName Hasegawa, Kazuhiro
	NRID 1000010227704 1000010227704 CreatorName Naiki, Hironobu
	NRID 1000040153770 1000040153770 researchmap permalink read0014440 read0014440 CreatorName Goto, Yuji
Description	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
Abstract	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.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	278(47)
Page	47016-47024
Date of Issued	2003-11
Language	English
Handle URL	https://hdl.handle.net/11094/71299
eISSN	1083351X
NCID	AA1202468X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M304473200
Access Rights	open access
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2003, 278(47), p. 47016-47024
DC.title	Amyloid Fibril Formation in the Context of Full-length Protein : EFFECTS OF PROLINE MUTATIONS ON THE AMYLOID FIBRIL FORMATION OF β2-MICROGLOBULIN
DC.creator	Chiba, Takeshi
	Hagihara, Yoshihisa
	Higurashi, Takashi
	Hasegawa, Kazuhiro
	Naiki, Hironobu
	Goto, Yuji
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2003-11
DC.identifier	https://doi.org/10.1074/jbc.M304473200
DC.description	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
DCTERMS.abstract	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.
DC.format	71299
citation_title	Amyloid Fibril Formation in the Context of Full-length Protein : EFFECTS OF PROLINE MUTATIONS ON THE AMYLOID FIBRIL FORMATION OF β2-MICROGLOBULIN
citation_author	Chiba, Takeshi
	Hagihara, Yoshihisa
	Higurashi, Takashi
	Hasegawa, Kazuhiro
	Naiki, Hironobu
	Goto, Yuji
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2003-11
citation_journal_title	Journal of Biological Chemistry
citation_volume	278
citation_issue	47
citation_firstpage	47016
citation_lastpage	47024
citation_doi	https://doi.org/10.1074/jbc.M304473200
citation_public_url	https://hdl.handle.net/11094/71299

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

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