ORBi: Kumita Janet R. - The extracellular chaperone clusterin potently inhibits human lysozyme amyloid formation by interacting with prefibrillar species

Reference : The extracellular chaperone clusterin potently inhibits human lysozyme amyloid formation...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/22327

Title :	The extracellular chaperone clusterin potently inhibits human lysozyme amyloid formation by interacting with prefibrillar species
Language :	English
Author, co-author :	Kumita, Janet R. [ > > ]
	Poon, Stephen [ > > ]
	Caddy, Gemma L. [ > > ]
	Hagan, C. L. [ > > ]
	Dumoulin, Mireille [Université de Liège - ULg > Département des sciences de la vie > Enzymologie et repliement des protéines >]
	Yerbury, Justin J. [ > > ]
	Stewart, Elise M. [ > > ]
	Robinson, Carol V. [ > > ]
	Wilson, Mark R. [ > > ]
	Dobson, Christopher M. [ > > ]
Publication date :	2007
Journal title :	Journal of Molecular Biology
Publisher :	Academic Press
Volume :	369
Pages :	157-161
Peer reviewed :	Yes (verified by ORBi)
Audience :	International
ISSN :	0022-2836
e-ISSN :	1089-8638
City :	London
Country :	United Kingdom
Abstract :	[en] We have studied the effects of the extracellular molecular chaperone, clusterin, on the in vitro aggregation of mutational variants of human lysozyme, including one associated with familial amyloid disease. The aggregation of the amyloidogenic variant I56T is inhibited significantly at clusterin to lysozyme ratios as low as 1:80 (i.e. one clusterin molecule per 80 lysozyme molecules). Experiments indicate that under the conditions where inhibition of aggregation occurs, clusterin does not bind detectably to the native or fibrillar states of lysozyme, or to the monomeric transient intermediate known to be a key species in the aggregation reaction. Rather, it seems to interact with oligomeric species that are present at low concentrations during the lag (nucleation) phase of the aggregation reaction. This behavior suggests that clusterin, and perhaps other extracellular chaperones, could have a key role in curtailing the potentially pathogenic effects of the misfolding and aggregation of proteins that, like lysozyme, are secreted into the extracellular environment.
Permalink :	http://hdl.handle.net/2268/22327

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