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Mechanism for retardation of amyloid fibril formation by sugars in Vλ6 protein
Author(s) -
Abe Masahiro,
Abe Yoshito,
Ohkuri Takatoshi,
Mishima Tomonori,
Monji Akira,
Kanba Shigenobu,
Ueda Tadashi
Publication year - 2013
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2228
Subject(s) - chemistry , osmolyte , fibril , amyloid (mycology) , amyloidosis , congo red , folding (dsp implementation) , trehalose , protein folding , biochemistry , amyloid fibril , biophysics , circular dichroism , thioflavin , amyloid β , organic chemistry , biology , alzheimer's disease , medicine , inorganic chemistry , disease , pathology , adsorption , electrical engineering , engineering
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.