Startseite Effect of molecular chaperones on aberrant protein oligomers in vitro: super-versus sub-stoichiometric chaperone concentrations
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Effect of molecular chaperones on aberrant protein oligomers in vitro: super-versus sub-stoichiometric chaperone concentrations

  • Sara Cappelli , Amanda Penco , Benedetta Mannini , Roberta Cascella , Mark R. Wilson , Heath Ecroyd , Xinyi Li , Joel N. Buxbaum , Christopher M. Dobson , Cristina Cecchi , Annalisa Relini und Fabrizio Chiti EMAIL logo
Veröffentlicht/Copyright: 18. Januar 2016
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 397 Heft 5

Abstract

Living systems protect themselves from aberrant proteins by a network of chaperones. We have tested in vitro the effects of different concentrations, ranging from 0 to 16 μm, of two molecular chaperones, namely αB-crystallin and clusterin, and an engineered monomeric variant of transthyretin (M-TTR), on the morphology and cytotoxicity of preformed toxic oligomers of HypF-N, which represent a useful model of misfolded protein aggregates. Using atomic force microscopy imaging and static light scattering analysis, all were found to bind HypF-N oligomers and increase the size of the aggregates, to an extent that correlates with chaperone concentration. SDS-PAGE profiles have shown that the large aggregates were predominantly composed of the HypF-N protein. ANS fluorescence measurements show that the chaperone-induced clustering of HypF-N oligomers does not change the overall solvent exposure of hydrophobic residues on the surface of the oligomers. αB-crystallin, clusterin and M-TTR can diminish the cytotoxic effects of the HypF-N oligomers at all chaperone concentration, as demonstrated by MTT reduction and Ca2+ influx measurements. The observation that the protective effect is primarily at all concentrations of chaperones, both when the increase in HypF-N aggregate size is minimal and large, emphasizes the efficiency and versatility of these protein molecules.

Keywords: molecular chaperones; protein aggregates; protein homeostasis; protein misfolding

Acknowledgments:

This work was supported with the ‘Fondi di Ateneo’ of the University of Florence, Italy.

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Received: 2015-9-10
Accepted: 2016-1-11
Published Online: 2016-1-18
Published in Print: 2016-5-1

©2016 by De Gruyter

Artikel in diesem Heft

  1. Frontmatter
  2. Review
  3. Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Effect of molecular chaperones on aberrant protein oligomers in vitro: super-versus sub-stoichiometric chaperone concentrations
  7. Two new isoforms of the human hepatoma-derived growth factor interact with components of the cytoskeleton
  8. Cell Biology and Signaling
  9. Activation of corticotropin releasing factor receptors up regulates collagen production by hepatic stellate cells via promoting p300 expression
  10. On the regulative role of the glutamate receptor in mitochondria
  11. Proteolysis
  12. Biomechanical and biochemical regulation of cathepsin K expression in endothelial cells converge at AP-1 and NF-κB
  13. New insights into the substrate specificity of macrophage elastase MMP-12
https://doi.org/10.1515/hsz-2015-0250
Schlagwörter für diesen Artikel
molecular chaperones; protein aggregates; protein homeostasis; protein misfolding

Artikel in diesem Heft

  1. Frontmatter
  2. Review
  3. Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Effect of molecular chaperones on aberrant protein oligomers in vitro: super-versus sub-stoichiometric chaperone concentrations
  7. Two new isoforms of the human hepatoma-derived growth factor interact with components of the cytoskeleton
  8. Cell Biology and Signaling
  9. Activation of corticotropin releasing factor receptors up regulates collagen production by hepatic stellate cells via promoting p300 expression
  10. On the regulative role of the glutamate receptor in mitochondria
  11. Proteolysis
  12. Biomechanical and biochemical regulation of cathepsin K expression in endothelial cells converge at AP-1 and NF-κB
  13. New insights into the substrate specificity of macrophage elastase MMP-12
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