Vibrational Approach to the Dynamics and Structure of Protein Amyloids

Abstract

Amyloid diseases, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s, are linked to a poorly understood progression of protein misfolding and aggregation events that culminate in tissue-selective deposition and human pathology. Elucidation of the mechanistic details of protein aggregation and the structural features of the aggregates is critical for a comprehensive understanding of the mechanisms of protein oligomerization and fibrillization. Vibrational spectroscopies, such as Fourier transform infrared (FTIR) and Raman, are powerful tools that are sensitive to the secondary structure of proteins and have been widely used to investigate protein misfolding and aggregation. We address the application of the vibrational approaches in recent studies of conformational dynamics and structural characteristics of protein oligomers and amyloid fibrils. In particular, introduction of isotope labelled carbonyl into a peptide backbone, and incorporation of the extrinsic unnatural amino acids with vibrational moieties on the side chain, have greatly expanded the ability of vibrational spectroscopy to obtain site-specific structural and dynamic information. The applications of these methods in recent studies of protein aggregation are also reviewed.

Characterization of Homogeneous and Heterogeneous Amyloid-β42 Oligomer Preparations with Biochemical Methods and Infrared Spectroscopy Reveals a Correlation between Infrared Spectrum and Oligomer Size

“…In addition to the main band near 1630 cm –1 , a smaller band at higher wavenumbers is also observed near 1685 cm –1 . Such a double-band feature in the amide I region of IR spectra for protein oligomers and early aggregates has been repeatedly reported and is consistent with the accepted IR signature for antiparallel β-sheets, 29 , 49 − 51 which is in line with theoretical considerations. 52 − 54 Furthermore, a combined experimental–computational study of mixtures of unlabeled and 13 C-labeled peptides concluded that each peptide molecule contributes at least two adjacent β-strands to the β-sheets of the oligomers, which is consistent with an antiparallel β-hairpin structure.…”

Heterochirality and Halogenation Control Phe-Phe Hierarchical Assembly

“…Because no halogen bond was observed in the crystal, and because Raman spectra of the crystal and the gel state displayed analogous signature, we inferred that the red shift was simply a manifestation of the hydrophobic environment surrounding the iodine atom as a result of self-assembly. 50 , 51 In the amide I region, the signal at 1664 cm –1 in the powder was shifted to 1685 cm –1 in the gel and crystal states, as a result of the extended hydrogen-bonding pattern between amides. 52 , 53 Similarly, the signal at 1250 cm 1 in the amide III region, resembling the β-sheet signature, was clearly visible in the gel and crystal states.…”

An extremely low-frequency magnetic field can affect CREB protein conformation which may have a role in neuronal activities including memory

“…These peaks have shifted to lower energies, which indicates a decrease in the molecular vibration due to a weaker strain on the vibrating molecules. Such as been specified above, proteins aggregation induces a shift to a lower frequency in the secondary structure [46,47]. This peak shift can also be supported by arguing that out of plane bending in combination with other molecular vibrations leave molecules more susceptible to be twisted by the magnetic field.…”