Similar toxicity of the oligomeric molten globule state and the prefibrillar oligomers

FEBS Lett. 2008 Jan 23;582(2):203-9. doi: 10.1016/j.febslet.2007.12.002. Epub 2007 Dec 17.

Abstract

We report that a mutant of human stefin B is in a molten globule conformation. It has all the spectroscopic characteristics for such a state. We also demonstrate that the molten globule is oligomeric, eluting on SEC within a similar MW range than the higher order oligomers of the wild type protein, which is confirmed by DLS and AFM. Both, the higher oligomers and the molten globule state bind ANS, implying a high degree of hydrophobic patches exposure and partial opening of the structure. Finally, we demonstrate that the oligomeric molten globule is as toxic as the prefibrillar aggregates obtained at acid pH or the higher order oligomers prepared at neutral pH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopolymers / chemistry*
  • Chromatography, Gel
  • Circular Dichroism
  • Cystatin B
  • Cystatins / chemistry
  • Cystatins / toxicity*
  • Humans
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Microscopy, Atomic Force
  • Protein Conformation

Substances

  • Biopolymers
  • CSTB protein, human
  • Cystatins
  • Cystatin B