title: Structural Rearrangement from Oligomer to Fibril Detected with FRET in a Designed Amphiphilic Peptide.
abstract: β-Sheet conformation is promoted in peptides with amphiphilic design, and stable β-turn formation is favored with the unnatural amino acid d-Pro followed by a flexible residue such as Gly. A 19-residue peptide (B3) was synthesized with alternating hydrophobic and hydrophilic residues connected by symmetrical d-Pro-Gly and Gly-d-Pro turns. B3 forms an oligomeric aggregate, rich in β-sheet conformation, that reversibly transforms into an unordered structure on heating, as evidenced by its temperature-dependent IR spectra. When a dansyl moiety was added to the N terminus of B3, the resulting peptide (B3D) can convert into a fibrillar structure after higher temperature incubation, as detected spectroscopically as well as by TEM. The fibrillization process involves an initial unfolding step monitored by the quenching of dansyl emission; in contrast, subsequent enhanced thioflavin T emission is seen on its binding to the fibril. A possible mechanism is proposed: B3D forms a low-temperature oligomer, which is at least partially unfolded by heat and subsequently reassembles more slowly as a fibril.
authors.affiliation: Department of Chemistry (M/C 111), University of Illinois at Chicago, 845 W. Taylor Street, Chicago, IL, 60607, USA.|Department of Pharmacy, Jiangsu Food and Pharmaceutical Science College, 4 E. Meicheng Rd. Huai'an, Jiangsu Province, 223005, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Chi
authors.affiliation: Department of Chemistry (M/C 111), University of Illinois at Chicago, 845 W. Taylor Street, Chicago, IL, 60607, USA.
authors.forename: Timothy A
authors.identifier: http://orcid.org/0000-0002-9380-3456
authors.initials: TA
authors.lastname: Keiderling
mesh_terms: D000595:Amino Acid Sequence; D052160:Benzothiazoles; D002942:Circular Dichroism; D031541:Fluorescence Resonance Energy Transfer; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared; D013696:Temperature; D013844:Thiazoles / Q000737:chemistry
chemical_list: D052160:Benzothiazoles; D010455:Peptides; D013844:Thiazoles; C009462:thioflavin T
keywords: FRET; UV/Vis spectroscopy; amphiphilic peptide design; protein folding; protein models; vibrational CD