Inhibition of β2-Microglobulin Amyloid Fibril Formation by α2-Macroglobulin

Ozawa, Daisaku; Hasegawa, Kazuhiro; Lee, Young-Ho; Sakurai, Kazumasa; Yanagi, Kotaro; Ookoshi, Tadakazu; Goto, Yuji; Naiki, Hironobu

doi:https://doi.org/10.1074/jbc.M110.167965

アクセス数:263件（2024-08-05 16:17 集計）

固定URL: https://hdl.handle.net/11094/71285

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タイトル	Inhibition of β2-Microglobulin Amyloid Fibril Formation by α2-Macroglobulin
著者	NRID 1000060554524 1000060554524 著者名 Ozawa, Daisaku
	NRID 1000060324159 1000060324159 著者名 Hasegawa, Kazuhiro
	NRID 1000070589431 1000070589431 著者名 Lee, Young-Ho
	NRID 1000010403015 1000010403015 著者名 Sakurai, Kazumasa
	著者名 Yanagi, Kotaro
	NRID 1000090362037 1000090362037 著者名 Ookoshi, Tadakazu
	NRID 1000040153770 1000040153770 researchmap permalink read0014440 read0014440 著者名 Goto, Yuji
	NRID 1000010227704 1000010227704 著者名 Naiki, Hironobu
内容	This research was originally published in the Journal of Biological Chemistry. Daisaku Ozawa, Kazuhiro Hasegawa, Young-Ho Lee, Kazumasa Sakurai, Kotaro Yanagi, Tadakazu Ookoshi, Yuji Goto and Hironobu Naiki. Inhibition of β2-Microglobulin Amyloid Fibril Formation by α2-Macroglobulin. J. Biol. Chem. 2011; 286, 9668-9676. © the American Society for Biochemistry and Molecular Biology
抄録	The relationship between various amyloidoses and chaperones is gathering attention. In patients with dialysis-related amyloidosis, α2-macroglobulin (α2M), an extracellular chaperone, forms a complex with β2-microglobulin (β2-m), a major component of amyloid fibrils, but the molecular mechanisms and biological implications of the complex formation remain unclear. Here, we found that α2M substoichiometrically inhibited the β2-m fibril formation at a neutral pH in the presence of SDS, a model for anionic lipids. Binding analysis showed that the binding affinity between α2M and β2-m in the presence of SDS was higher than that in the absence of SDS. Importantly, SDS dissociated tetrameric α2M into dimers with increased surface hydrophobicity. Western blot analysis revealed that both tetrameric and dimeric α2M interacted with SDS-denatured β2-m. At a physiologically relevant acidic pH and in the presence of heparin, α2M was also dissociated into dimers, and both tetrameric and dimeric α2M interacted with β2-m, resulting in the inhibition of fibril growth reaction. These results suggest that under conditions where native β2-m is denatured, tetrameric α2M is also converted to dimeric form with exposed hydrophobic surfaces to favor the hydrophobic interaction with denatured β2-m, thus dimeric α2M as well as tetrameric α2M may play an important role in controlling β2-m amyloid fibril formation.
出版者	American Society for Biochemistry and Molecular Biology
収録物名	Journal of Biological Chemistry
巻(号)	286(11)
ページ	9668-9676
刊行年月	2011-03
言語	英語
ハンドルURL	https://hdl.handle.net/11094/71285
eISSN	1083351X
NCID	AA1202454X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1074/jbc.M110.167965
アクセス権	open access
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2011, 286(11), p. 9668-9676
DC.title	Inhibition of β2-Microglobulin Amyloid Fibril Formation by α2-Macroglobulin
DC.creator	Ozawa, Daisaku
	Hasegawa, Kazuhiro
	Lee, Young-Ho
	Sakurai, Kazumasa
	Yanagi, Kotaro
	Ookoshi, Tadakazu
	Goto, Yuji
	Naiki, Hironobu
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2011-03
DC.identifier	https://doi.org/10.1074/jbc.M110.167965
DC.description	This research was originally published in the Journal of Biological Chemistry. Daisaku Ozawa, Kazuhiro Hasegawa, Young-Ho Lee, Kazumasa Sakurai, Kotaro Yanagi, Tadakazu Ookoshi, Yuji Goto and Hironobu Naiki. Inhibition of β2-Microglobulin Amyloid Fibril Formation by α2-Macroglobulin. J. Biol. Chem. 2011; 286, 9668-9676. © the American Society for Biochemistry and Molecular Biology
DCTERMS.abstract	The relationship between various amyloidoses and chaperones is gathering attention. In patients with dialysis-related amyloidosis, α2-macroglobulin (α2M), an extracellular chaperone, forms a complex with β2-microglobulin (β2-m), a major component of amyloid fibrils, but the molecular mechanisms and biological implications of the complex formation remain unclear. Here, we found that α2M substoichiometrically inhibited the β2-m fibril formation at a neutral pH in the presence of SDS, a model for anionic lipids. Binding analysis showed that the binding affinity between α2M and β2-m in the presence of SDS was higher than that in the absence of SDS. Importantly, SDS dissociated tetrameric α2M into dimers with increased surface hydrophobicity. Western blot analysis revealed that both tetrameric and dimeric α2M interacted with SDS-denatured β2-m. At a physiologically relevant acidic pH and in the presence of heparin, α2M was also dissociated into dimers, and both tetrameric and dimeric α2M interacted with β2-m, resulting in the inhibition of fibril growth reaction. These results suggest that under conditions where native β2-m is denatured, tetrameric α2M is also converted to dimeric form with exposed hydrophobic surfaces to favor the hydrophobic interaction with denatured β2-m, thus dimeric α2M as well as tetrameric α2M may play an important role in controlling β2-m amyloid fibril formation.
DC.format	71285
citation_title	Inhibition of β2-Microglobulin Amyloid Fibril Formation by α2-Macroglobulin
citation_author	Ozawa, Daisaku
	Hasegawa, Kazuhiro
	Lee, Young-Ho
	Sakurai, Kazumasa
	Yanagi, Kotaro
	Ookoshi, Tadakazu
	Goto, Yuji
	Naiki, Hironobu
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	英語
citation_date	2011-03
citation_journal_title	Journal of Biological Chemistry
citation_volume	286
citation_issue	11
citation_firstpage	9668
citation_lastpage	9676
citation_doi	https://doi.org/10.1074/jbc.M110.167965
citation_public_url	https://hdl.handle.net/11094/71285

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