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:https://doi.org/10.1074/jbc.M117.813097

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

Nitani, Ayame; Muta, Hiroya; Adachi, Masayuki et al.

Journal of Biological Chemistry, 2017, 292(52), 21219-21230

Number of Access:777（2025-07-02 22:39 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/71272

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Title	Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation
Creator	CreatorName Nitani, Ayame
	CreatorName Muta, Hiroya
	CreatorName Adachi, Masayuki
	NRID 1000040746335 1000040746335 CreatorName So, Masatomo
	NRID 1000020432495 1000020432495 CreatorName Sasahara, Kenji
	NRID 1000010403015 1000010403015 CreatorName Sakurai, Kazumasa
	NRID 1000000432493 1000000432493 CreatorName Chatani, Eri
	NRID 1000000259912 1000000259912 CreatorName Naoe, Kazumitsu
	NRID 1000090252626 1000090252626 researchmap permalink read0042771 read0042771 Scopus Author ID 35563683500 35563683500 CreatorName Ogi, Hirotsugu
	CreatorName Hal, Damien
	NRID 1000040153770 1000040153770 researchmap permalink read0014440 read0014440 CreatorName Goto, Yuji
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
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.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	292(52)
Page	21219-21230
Date of Issued	2017-11
Language	English
Handle URL	https://hdl.handle.net/11094/71272
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M117.813097
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. 2017, 292(52), p. 21219-21230
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	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2017-11
DC.identifier	https://doi.org/10.1074/jbc.M117.813097
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.
DC.format	71272
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	English
citation_date	2017-11
citation_journal_title	Journal of Biological Chemistry
citation_volume	292
citation_issue	52
citation_firstpage	21219
citation_lastpage	21230
citation_doi	https://doi.org/10.1074/jbc.M117.813097
citation_public_url	https://hdl.handle.net/11094/71272

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

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