Mechanism by which the amyloid-like fibrils of a beta 2-microglobulin fragment are induced by fluorine-substituted alcohols.
Although the formation of an alpha-helix or partial unfolding of proteins has been suggested to be important for amyloid fibrils to form in alcohols, the exact mechanism involved remains elusive. To obtain further insight into the development of amyloid fibrils, we used a 22-residue peptide, K3, corresponding to Ser20 to Lys41 of intact beta2-microglobulin. Although K3 formed an alpha-helix at high concentrations of 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) in 10 mM HCl (pH approximately 2), the helical content was not high, indicating a low preference to do so. The partly alpha-helical conformation was converted with time into a highly ordered beta-sheet with a fibrillar morphology as revealed by atomic force microscopy. Importantly, the TFE and HFIP-induced fibrillation exhibited a concentration dependence with a maximum at approximately 20 and approximately 10% (v/v), respectively, slightly below the concentrations at which these alcohols form dynamic clusters. Focusing on the similarity of the effects of alcohol on proteins with those of sodium dodecyl sulfate (SDS), we examined the effects of SDS on K3. SDS also induced fibrils to form with a maximum at approximately 4 mM, slightly below the critical micelle concentration. These results indicate that, with an increase in the concentration of hydrophobic cosolvent (TFE, HFIP, or SDS), a delicate balance of decreasing hydrophobic interactions and increasing polar interactions (i.e. H-bonds) in and between peptides leads to the formation of ordered fibrils with a bell-shaped concentration dependence.
Yamaguchi
Kei-ichi
K
Institute for Protein Research, Osaka University, and CREST, Japan Science and Technology Agency, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
Naiki
Hironobu
H
Goto
Yuji
Y
D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000737:chemistry; D020005:Propanols / Q000737:chemistry*; D012997:Solvents; D014270:Trifluoroethanol / Q000737:chemistry*; D001613:beta 2-Microglobulin / Q000096:biosynthesis* / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated
D000682:Amyloid; D005461:Fluorine; D010446:Peptide Fragments; D020005:Propanols; D012997:Solvents; D014270:Trifluoroethanol; D001613:beta 2-Microglobulin; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated