Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation

Nitani, Ayame; Muta, Hiroya; Adachi, Masayuki; So, Masatomo; Sasahara, Kenji; Sakurai, Kazumasa; Chatani, Eri; Naoe, Kazumitsu; Ogi, Hirotsugu; Hal, Damien; Goto, Yuji

doi:info:doi/10.1074/jbc.M117.813097

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タイトル	Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation
著者	Nitani, Ayame Nitani, Ayame
	Muta, Hiroya Muta, Hiroya
	Adachi, Masayuki Adachi, Masayuki
	So, Masatomo So, Masatomo
	Sasahara, Kenji Sasahara, Kenji
	Sakurai, Kazumasa Sakurai, Kazumasa
	Chatani, Eri Chatani, Eri
	Naoe, Kazumitsu Naoe, Kazumitsu
	Ogi, Hirotsugu Ogi, Hirotsugu
	Hal, Damien Hal, Damien
	Goto, Yuji Goto, Yuji
内容	This research was originally published in the Journal of Biological Chemistry. Ayame Nitani, Hiroya Muta, Masayuki Adachi, Masatomo So, Kenji Sasahara, Kazumasa Sakurai, Eri Chatani, Kazumitsu Naoe, Hirotsugu Ogi, Damien Hall, and Yuji Goto. Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation. J. Biol. Chem. 2017; 292, 21219-21230 © the American Society for Biochemistry and Molecular Biology
抄録	Heparin, a biopolymer possessing high negative charge density, is known to accelerate amyloid fibrillation by various proteins. Using hen egg white lysozyme, we studied the effects of heparin on protein aggregation at low pH, raised temperature, and applied ultrasonic irradiation, conditions under which amyloid fibrillation was promoted. Heparin exhibited complex bimodal concentration-dependent effects, either accelerating or inhibiting fibrillation at pH 2.0 and 60 °C. At concentrations lower than 20 μg/ml, heparin accelerated fibrillation through transient formation of hetero-oligomeric aggregates. Between 0.1 and 10 mg/ml, heparin rapidly induced amorphous heteroaggregation with little to no accompanying fibril formation. Above 10 mg/ml, heparin again induced fibrillation after a long lag time preceded by oligomeric aggregate formation. Compared with studies performed using monovalent and divalent anions, the results suggest two distinct mechanisms of heparin-induced fibrillation. At low heparin concentrations, initial hen egg white lysozyme cluster formation and subsequent fibrillation is promoted by counter ion binding and screening of repulsive charges. At high heparin concentrations, fibrillation is caused by a combination of salting out and macromolecular crowding effects probably independent of protein net charge. Both fibrillation mechanisms compete against amorphous aggregation, producing a complex heparin concentration–dependent phase diagram. Moreover, the results suggest an active role for amorphous oligomeric aggregates in triggering fibrillation, whereby breakdown of supersaturation takes place through heterogeneous nucleation of amyloid on amorphous aggregates.
公開者	American Society for Biochemistry and Molecular Biology
掲載誌名	Journal of Biological Chemistry
巻	292
号	52
開始ページ	21219
終了ページ	21230
刊行年月	2017-11
ISSN	1083351X
NCID	AA1202441X
DOI	info:doi/10.1074/jbc.M117.813097
URL	http://hdl.handle.net/11094/71272
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII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.292(52) P.21219-P.21230
DC.title	Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation
DC.creator	Nitani, Ayame
	Muta, Hiroya
	Adachi, Masayuki
	So, Masatomo
	Sasahara, Kenji
	Sakurai, Kazumasa
	Chatani, Eri
	Naoe, Kazumitsu
	Ogi, Hirotsugu
	Hal, Damien
	Goto, Yuji
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language" scheme="DCTERMS.RFC1766	英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2017-11
DC.identifier	info:doi/10.1074/jbc.M117.813097
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/71272
DC.description	This research was originally published in the Journal of Biological Chemistry. Ayame Nitani, Hiroya Muta, Masayuki Adachi, Masatomo So, Kenji Sasahara, Kazumasa Sakurai, Eri Chatani, Kazumitsu Naoe, Hirotsugu Ogi, Damien Hall, and Yuji Goto. Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation. J. Biol. Chem. 2017; 292, 21219-21230 © the American Society for Biochemistry and Molecular Biology
DCTERMS.abstract	Heparin, a biopolymer possessing high negative charge density, is known to accelerate amyloid fibrillation by various proteins. Using hen egg white lysozyme, we studied the effects of heparin on protein aggregation at low pH, raised temperature, and applied ultrasonic irradiation, conditions under which amyloid fibrillation was promoted. Heparin exhibited complex bimodal concentration-dependent effects, either accelerating or inhibiting fibrillation at pH 2.0 and 60 °C. At concentrations lower than 20 μg/ml, heparin accelerated fibrillation through transient formation of hetero-oligomeric aggregates. Between 0.1 and 10 mg/ml, heparin rapidly induced amorphous heteroaggregation with little to no accompanying fibril formation. Above 10 mg/ml, heparin again induced fibrillation after a long lag time preceded by oligomeric aggregate formation. Compared with studies performed using monovalent and divalent anions, the results suggest two distinct mechanisms of heparin-induced fibrillation. At low heparin concentrations, initial hen egg white lysozyme cluster formation and subsequent fibrillation is promoted by counter ion binding and screening of repulsive charges. At high heparin concentrations, fibrillation is caused by a combination of salting out and macromolecular crowding effects probably independent of protein net charge. Both fibrillation mechanisms compete against amorphous aggregation, producing a complex heparin concentration–dependent phase diagram. Moreover, the results suggest an active role for amorphous oligomeric aggregates in triggering fibrillation, whereby breakdown of supersaturation takes place through heterogeneous nucleation of amyloid on amorphous aggregates.
citation_title	Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation
citation_author	Nitani, Ayame
	Muta, Hiroya
	Adachi, Masayuki
	So, Masatomo
	Sasahara, Kenji
	Sakurai, Kazumasa
	Chatani, Eri
	Naoe, Kazumitsu
	Ogi, Hirotsugu
	Hal, Damien
	Goto, Yuji
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	英語
citation_date	2017-11
citation_journal_title	Journal of Biological Chemistry
citation_volume	292
citation_issue	52
citation_firstpage	21219
citation_lastpage	21230
citation_issn	1083351X
citation_doi	info:doi/10.1074/jbc.M117.813097
citation_public_url	http://hdl.handle.net/11094/71272

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