Skip to main content
Article
The extracellular chaperone clusterin potently inhibits human lysozyme amyloid formation by interacting with prefibrillar species
Faculty of Science - Papers (Archive) (2007)
  • Mark R Wilson, University of Wollongong
  • Justin Yerbury
  • Stephen Poon, University of Wollongong
  • Christopher Dobson
  • C V Robinson
  • Elise M Stewart, University of Wollongong
  • Janet R Kumita, University of Cambridge
  • Mireille Dumoulin, University of Cambridge
  • Gemma L Caddy, University of Cambridge
  • Christine L Hagan, University of Cambridge
Abstract
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, 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 behaviour suggests that clusterin, and perhaps other extracellular chaperones, could have a key role in limiting the potentially pathogenic effects of the misfolding and aggregation of proteins that, like lysozyme, are secreted into the extracellular environment.
Keywords
  • extracellular,
  • chaperone,
  • clusterin,
  • potently,
  • inhibits,
  • human,
  • lysozyme,
  • amyloid,
  • formation,
  • interacting,
  • prefibrillar,
  • species
Publication Date
January 1, 2007
Publisher Statement
Kumita, J. R., Poon, S., Caddy, G. L., Hagan, C. L., Dumoulin, M., Yerbury, J., Stewart, E. M., Robinson, C., Wilson, M. R. & Dobson, C. (2007). The extracellular chaperone clusterin potently inhibits human lysozyme amyloid formation by interacting with prefibrillar species. Journal of Molecular Biology, 369 (1), 157-167.
Citation Information
Mark R Wilson, Justin Yerbury, Stephen Poon, Christopher Dobson, et al.. "The extracellular chaperone clusterin potently inhibits human lysozyme amyloid formation by interacting with prefibrillar species" Faculty of Science - Papers (Archive) (2007)
Available at: http://works.bepress.com/mark_wilson/36/