Small heat-shock proteins and clusterin: intra- and extracellular molecular chaperones with a common mechanism of action and function?

IUBMB Life. 2003 Dec;55(12):661-8. doi: 10.1080/15216540310001640498.


Small heat-shock proteins (sHsps) and clusterin are molecular chaperones that share many functional similarities despite their lack of significant sequence similarity. These functional similarities, and some differences, are discussed. sHsps are ubiquitous intracellular proteins whereas clusterin is generally found extracellularly. Both chaperones potently prevent the amorphous aggregation and precipitation of target proteins under stress conditions such as elevated temperature, reduction and oxidation. In doing so, they act on the slow, off-folding protein pathway. The conformational dynamism and aggregated state of both proteins may be crucial for their chaperone function. Subunit exchange is likely to be important in regulating chaperone action; the dissociated form of the protein is probably the chaperone-active species rather than the aggregated state. They both exert their chaperone action without the need for hydrolysis of ATP and have little ability to refold target proteins. Increased expression of sHsps and clusterin accompanies a range of diseases that arise from protein misfolding and deposition of highly structured protein aggregates known as amyloid fibrils, e.g., Alzheimer's, Creutzfeldt-Jakob and Parkinson's diseases. The interaction of sHsps and clusterin with fibril-forming species is discussed along with their ability to prevent fibril formation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chemical Precipitation
  • Clusterin
  • Glycoproteins / metabolism*
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Models, Biological
  • Molecular Chaperones / metabolism*
  • Molecular Weight
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Tissue Distribution


  • CLU protein, human
  • Clusterin
  • Glycoproteins
  • Heat-Shock Proteins
  • Molecular Chaperones