title: 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: Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Masahiro
authors: M
authors: Abe
authors: Yoshito
authors: Y
authors: Abe
authors: Takatoshi
authors: T
authors: Ohkuri
authors: Tomonori
authors: T
authors: Mishima
authors: Akira
authors: A
authors: Monji
authors: Shigenobu
authors: S
authors: Kanba
authors: Tadashi
authors: T
authors: Ueda
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D005947:Glucose / Q000737:chemistry / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D009994:Osmolar Concentration; D011489:Protein Denaturation; D017510:Protein Folding; D013056:Spectrophotometry, Ultraviolet; D013395:Sucrose / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000682:Amyloid; D013395:Sucrose; D005947:Glucose
references: J Clin Invest. 1993 Sep;92(3):1243-52
references: 8376584
references: J Mol Biol. 2005 Mar 18;347(1):159-68
references: 15733925
references: Science. 2002 Mar 1;295(5560):1719-22
references: 11872841
references: J Biol Chem. 2000 Jan 21;275(3):1570-4
references: 10636846
references: J Mol Biol. 2009 Oct 2;392(4):1033-43
references: 19647748
references: Biochemistry. 1997 Jul 22;36(29):8977-91
references: 9220986
references: J Biomol NMR. 2001 Nov;21(3):249-61
references: 11775741
references: J Biol Chem. 1981 Jul 25;256(14):7193-201
references: 7251592
references: Biochemistry. 1982 Dec 7;21(25):6536-44
references: 7150574
references: Biochem Biophys Res Commun. 2007 May 11;356(3):769-72
references: 17382294
references: J Biochem. 2001 Oct;130(4):491-6
references: 11574068
references: Protein Sci. 2006 Oct;15(10):2448-52
references: 16963644
references: IUBMB Life. 2010 Dec;62(12):891-5
references: 21190292
references: Proteins. 2008 Dec;73(4):802-13
references: 18498104
references: Neurobiol Dis. 2005 Oct;20(1):74-81
references: 16137568
references: Biochim Biophys Acta. 2004 May 6;1698(2):131-53
references: 15134647
references: J Struct Biol. 2000 Jun;130(2-3):280-9
references: 10940232
references: Biochim Biophys Acta. 2007 Jul;1774(7):928-35
references: 17581805
references: Trends Biochem Sci. 1999 Sep;24(9):329-32
references: 10470028
references: Protein Sci. 1996 Feb;5(2):372-81
references: 8745416
references: Nat Med. 2004 Feb;10(2):148-54
references: 14730359
references: Annu Rev Biochem. 1992;61:947-75
references: 1497327
references: Angew Chem Int Ed Engl. 2004 Nov 5;43(43):5780-5
references: 15523735
references: Biochemistry. 2009 Sep 22;48(37):8908-19
references: 19637920
references: FEBS Lett. 2004 Apr 23;564(1-2):121-5
references: 15094052
references: Int J Biochem Cell Biol. 2002 Feb;34(2):136-47
references: 11809416
references: Curr Opin Struct Biol. 1998 Feb;8(1):101-6
references: 9519302
references: Biol Pharm Bull. 2002 Mar;25(3):375-8
references: 11913537
references: Anal Biochem. 1989 Mar;177(2):244-9
references: 2729542
references: Science. 1982 Sep 24;217(4566):1214-22
references: 7112124
references: Biochem Biophys Res Commun. 2010 Jan 1;391(1):615-20
references: 19932684