Mechanism for retardation of amyloid fibril formation by sugars in Vλ6 protein

Masahiro Abe, Yoshito Abe, Takatoshi Ohkuri, Tomonori Mishima, Akira Monji, Shigenobu Kanba, Tadashi Ueda

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Sugars, which function as osmolytes within cells, retard the amyloid fibril formation of the amyloidosis peptides and proteins. To examine the mechanism of this retardation in detail, we analyzed the effect of sugars (trehalose, sucrose, and glucose) on the polypeptide chains in 3Hmut Wil, which is formed by the mutation of three His residues in Wil mutant as a cause of amyloid light-chain (AL) amyloidosis, at pH 2, a pH condition under which 3Hmut Wil was almost denatured. Sugars caused the folding of 3Hmut Wil so that its polypeptide chains adopted a native-like rather than a denatured conformation, as suggested by tryptophan fluorescence, CD spectroscopy, and heteronuclear NMR. Furthermore, these sugars promoted the folding to a native-like conformation according to the effect of preferential hydration rather than direct interaction. However, the type of sugar had no effect on the elongation of amyloid fibrils. Therefore, it was concluded that sugar affected the thermodynamic stability of 3Hmut Wil but not the elongation of amyloid fibrils.

Original languageEnglish
Pages (from-to)467-474
Number of pages8
JournalProtein Science
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 1 2013

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Amyloid
Sugars
Amyloidosis
Peptides
Proteins
Biomolecular Nuclear Magnetic Resonance
Trehalose
Conformations
Elongation
Fluorescence Spectrometry
Thermodynamics
Tryptophan
Sucrose
Light
Glucose
Hydration
Mutation
Thermodynamic stability
Fluorescence
Nuclear magnetic resonance

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Mechanism for retardation of amyloid fibril formation by sugars in Vλ6 protein. / Abe, Masahiro; Abe, Yoshito; Ohkuri, Takatoshi; Mishima, Tomonori; Monji, Akira; Kanba, Shigenobu; Ueda, Tadashi.

In: Protein Science, Vol. 22, No. 4, 01.04.2013, p. 467-474.

Research output: Contribution to journalArticle

Abe, Masahiro ; Abe, Yoshito ; Ohkuri, Takatoshi ; Mishima, Tomonori ; Monji, Akira ; Kanba, Shigenobu ; Ueda, Tadashi. / Mechanism for retardation of amyloid fibril formation by sugars in Vλ6 protein. In: Protein Science. 2013 ; Vol. 22, No. 4. pp. 467-474.
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AU - Kanba, Shigenobu

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