Structural studies reveal that the diverse morphology of β2-microglobulin aggregates is a reflection of different molecular architectures

J. Kardos, Daichi Okuno, Tomoji Kawai, Yoshihisa Hagihara, Noboru Yumoto, Teizo Kitagawa, P. Závodszky, Hironobu Naiki, Yuji Goto

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Amyloid deposition accompanies over 20 degenerative diseases in human, including Alzheimer's, Parkinson's, and prion diseases. Recent studies revealed the importance of other type of protein aggregates, e.g., non-specific aggregates, protofibrils, and small oligomers in the development of such diseases and proved their increased toxicity for living cells in comparison with mature amyloid fibrils. We carried out a comparative structural analysis of different monomeric and aggregated states of β2-microglobulin, a protein responsible for hemodialysis-related amyloidosis. We investigated the structure of the native and acid-denatured states, as well as that of mature fibrils, immature fibrils, amorphous aggregates, and heat-induced filaments, prepared under various in vitro conditions. Infrared spectroscopy demonstrated that the β-sheet compositions of immature fibrils, heat-induced filaments and amorphous aggregates are characteristic of antiparallel intermolecular β-sheet structure while mature fibrils are different from all others suggesting a unique overall structure and assembly. Filamentous aggregates prepared by heat treatment are of importance in understanding the in vivo disease because of their stability under physiological conditions, where amyloid fibrils and protofibrils formed at acidic pH depolymerize. Atomic force microscopy of heat-induced filaments represented a morphology similar to that of the low pH immature fibrils. At a pH close to the pI of the protein, amorphous aggregates were formed readily with association of the molecules in native-like conformation, followed by formation of intermolecular β-sheet structure in a longer time-scale. Extent of the core buried from the solvent in the various states was investigated by H/D exchange of the amide protons.

Original languageEnglish
Pages (from-to)108-120
Number of pages13
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1753
Issue number1
DOIs
Publication statusPublished - Nov 10 2005

Fingerprint

Hot Temperature
Amyloid
Prion Diseases
Atomic Force Microscopy
Amyloidosis
Amides
Prions
Parkinson Disease
Renal Dialysis
Protons
Spectrum Analysis
Alzheimer Disease
Oligomers
Structural analysis
Toxicity
Conformations
Infrared spectroscopy
Atomic force microscopy
Proteins
Acids

Keywords

  • β-microglobulin
  • Amyloid formation
  • Fourier transform infrared spectroscopy
  • Hydrogen-deuterium exchange
  • Protein aggregation
  • Secondary structure

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics

Cite this

Structural studies reveal that the diverse morphology of β2-microglobulin aggregates is a reflection of different molecular architectures. / Kardos, J.; Okuno, Daichi; Kawai, Tomoji; Hagihara, Yoshihisa; Yumoto, Noboru; Kitagawa, Teizo; Závodszky, P.; Naiki, Hironobu; Goto, Yuji.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1753, No. 1, 10.11.2005, p. 108-120.

Research output: Contribution to journalArticle

Kardos, J. ; Okuno, Daichi ; Kawai, Tomoji ; Hagihara, Yoshihisa ; Yumoto, Noboru ; Kitagawa, Teizo ; Závodszky, P. ; Naiki, Hironobu ; Goto, Yuji. / Structural studies reveal that the diverse morphology of β2-microglobulin aggregates is a reflection of different molecular architectures. In: Biochimica et Biophysica Acta - Proteins and Proteomics. 2005 ; Vol. 1753, No. 1. pp. 108-120.
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