Structural perturbation of alpha-crystallin and its chaperone-like activity

Int J Biol Macromol. 1998 May-Jun;22(3-4):271-81. doi: 10.1016/s0141-8130(98)00025-7.

Abstract

alpha-Crystallin is a multimeric lenticular protein that has recently been shown to be expressed in several non-lenticular tissues as well. It is shown to prevent aggregation of non-native proteins as a molecular chaperone. By using a non-thermal aggregation model, we could show that this process is temperature-dependent. We investigated the chaperone-like activity of alpha-crystallin towards photo-induced aggregation of gamma-crystallin, aggregation of insulin and on the refolding induced aggregation of beta- and gamma-crystallins. We observed that alpha-crystallin could prevent photo-aggregation of gamma-crystallin and this chaperone-like activity of alpha-crystallin is enhanced several fold at temperatures above 30 degrees C. This enhancement parallels the exposure of its hydrophobic surfaces as a function of temperature, probed using hydrophobic fluorescent probes such as pyrene and 8-anilinonaphthalene-1-sulfonate. We, therefore, concluded that alpha-crystallin prevents the aggregation of other proteins by providing appropriately placed hydrophobic surfaces; a structural transition above 30 degrees C involving enhanced or re-organized hydrophobic surfaces of alpha-crystallin is important for its chaperone-like activity. We also addressed the issue of conformational aspects of target proteins and found that their aggregation prone molten globule states bind to alpha-crystallin. We trace these developments and discuss some new lines that suggest the role of tertiary structural aspects in the chaperone process.

Publication types

  • Review

MeSH terms

  • Animals
  • Crystallins / chemistry*
  • Crystallins / metabolism*
  • Crystallins / radiation effects
  • Dithiothreitol
  • In Vitro Techniques
  • Insulin / chemistry
  • Insulin / metabolism
  • Macromolecular Substances
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / metabolism*
  • Molecular Chaperones / radiation effects
  • Photochemistry
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • Temperature

Substances

  • Crystallins
  • Insulin
  • Macromolecular Substances
  • Molecular Chaperones
  • Dithiothreitol