Beta2-microglobulin can be refolded into a native state from ex vivo amyloid fibrils

Eur J Biochem. 1998 Nov 15;258(1):61-7. doi: 10.1046/j.1432-1327.1998.2580061.x.

Abstract

Beta2-microglobulin fibrils have been extracted from the femoral head of a patient who has been under chronic haemodialysis for 11 years. The primary structure of the N-terminal portion of the protein and mass determination by electrospray mass spectrometry demonstrate that beta2-microglobulin, extracted as fibrils by the water extraction procedure, was not glycated and that Asn17 was not deamidated. Limited proteolysis was observed in more than 20% of beta2-microglobulin molecules and the main cleavage sites were at the C-terminus of Lys6 and Tyr10. Beta2-microglobulin from fibrils has been purified by gel filtration in 6 M Gdn/HCl and submitted to a refolding procedure. The refolding conditions have been determined through the study of the unfolding pathway of the native protein. Beta2-microglobulin is stable at neutral pH where it displays a lower tendency to self-aggregate than in acidic conditions. Pulse dilution and extensive dialysis in refolding buffer at pH 7.5 yields beta2-microglobulin with a tertiary structure identical to that of the native form. The CD spectrum in the near-ultraviolet region and the spectrum of the intrinsic fluorescence of Trp overlap those of the native protein, but the CD spectrum in the far-ultraviolet region is affected by the contribution of oligomers created by beta2-microglobulin fragments that reduce the positive light polarisation at 205 nm typical of native beta2-microglobulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Chromatography, Gel
  • Circular Dichroism
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Microscopy, Electron
  • Molecular Sequence Data
  • Molecular Weight
  • Protein Folding*
  • Spectrometry, Fluorescence
  • beta 2-Microglobulin / chemistry*
  • beta 2-Microglobulin / isolation & purification

Substances

  • beta 2-Microglobulin