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: Hongchun Li, Shuji Ye, Feng Wei, Sulan Ma, Yi Luo
• Journal: Langmuir : the ACS journal of surfaces and colloids (Langmuir) Vol. 28 Issue 49 Pg. 16979-88 (Dec 11 2012) ISSN: 1520-5827 [Electronic] United States
• PMID: 23116165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipid Bilayers
• Peptide Fragments
• Phosphatidylglycerols
• Prions
• prion protein (118-135)
• 1-palmitoyl-2-oleoylglycero-3-phosphoglycerol

Topics

• Amino Acid Sequence
• Lipid Bilayers (chemistry)
• Models, Molecular
• Molecular Sequence Data
• Peptide Fragments (chemistry)
• Phosphatidylglycerols (chemistry)
• Prions (chemistry)
• Protein Binding
• Protein Structure, Secondary
• Spectroscopy, Fourier Transform Infrared
• Vibration