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

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.

• Authors: Masahiro Abe, Yoshito Abe, Takatoshi Ohkuri, Tomonori Mishima, Akira Monji, Shigenobu Kanba, Tadashi Ueda
• Journal: Protein science : a publication of the Protein Society (Protein Sci) Vol. 22 Issue 4 Pg. 467-74 (Apr 2013) ISSN: 1469-896X [Electronic] United States
• PMID: 23389799 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 The Protein Society.

Chemical References

• Amyloid
• Sucrose
• Glucose

Topics

• Amyloid (chemistry, metabolism)
• Glucose (chemistry, pharmacology)
• Nuclear Magnetic Resonance, Biomolecular
• Osmolar Concentration
• Protein Denaturation
• Protein Folding
• Spectrophotometry, Ultraviolet
• Sucrose (chemistry, pharmacology)