title: In situ molecular-level insights into the interfacial structure changes of membrane-associated prion protein fragment [118-135] investigated by sum frequency generation vibrational spectroscopy.
abstract: Protein aggregation is associated with many "protein deposition diseases". A precise molecular detail of the conformational transitions of such a membrane-associated protein structure is critical to understand the disease mechanism and develop effective treatments. One potential model peptide for studying the mechanism of protein deposition diseases is prion protein fragment [118-135] (PrP118-135), which shares homology with the C-terminal domain of the Alzheimer's β-amyloid peptide. In this study, sum frequency generation vibrational spectroscopy (SFG-VS) has been applied to characterize interactions between PrP118-135 and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) lipid bilayer in situ. The conformation change and orientation of PrP118-135 in lipid bilayers have been determined using SFG spectra with different polarization combinations. It is found that low-concentration PrP118-135 predominantly adopts α-helical structure but with tiny β-sheet structure. With the PrP118-135 concentration increasing, the molecular number ratio of parallel β-sheet structure increases and reaches about 44% at a concentration of 0.10 mg/mL, indicating the formation of abnormally folded scrapie isoforms. The α-helical structure inserts into the lipid bilayer with a tilt angle of ~32° versus the surface normal, while the β-sheet structure lies down on the lipid bilayer with the tilt and twist angle both of 90°. The 3300 cm(-1) N-H stretching signal in psp spectra arises from α-helical structure at low PrP concentration and from the β-sheet structure at high PrP concentration. Results from this study will provide an in-depth insight into the early events in the aggregation of PrP in cell membrane.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, and Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui, People's Republic of China 230026.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Li
authors.forename: Shuji
authors.initials: S
authors.lastname: Ye
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Sulan
authors.initials: S
authors.lastname: Ma
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
mesh_terms: D000595:Amino Acid Sequence; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D014732:Vibration
chemical_list: D008051:Lipid Bilayers; D010446:Peptide Fragments; D010715:Phosphatidylglycerols; D011328:Prions; C417023:prion protein (118-135); C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol