| 1. |
- Baldassarre, Maurizio, et al.
(author)
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Amyloid beta-peptides 1-40 and 1-42 form oligomers with mixed beta-sheets
- 2017
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In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 8:12, s. 8247-8254
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Journal article (peer-reviewed)abstract
- Two main amyloid-beta peptides of different length (A beta(40) and A beta(42)) are involved in Alzheimer's disease. Their relative abundance is decisive for the severity of the disease and mixed oligomers may contribute to the toxic species. However, little is know about the extent of mixing. To study whether A beta(40) and A beta(42) co-aggregate, we used Fourier transform infrared spectroscopy in combination with C-13-labeling and spectrum calculation and focused on the amide I vibration, which is sensitive to backbone structure. Mixtures of monomeric labeled A beta(40) and unlabeled A beta(42) (and vice versa) were co-incubated for similar to 20 min and their infrared spectrum recorded. The position of the main C-13-amide I' band shifted to higher wavenumbers with increasing admixture of C-12-peptide due to the presence of C-12-amides in the vicinity of C-13-amides. The results indicate that A beta(40) and A beta(42) form mixed oligomers with a largely random distribution of A beta(40) and A beta(42) strands in their beta-sheets. The structures of the mixed oligomers are intermediate between those of the pure oligomers. There is no indication that one of the peptides forces the backbone structure of its oligomers on the other peptide when they are mixed as monomers. We also demonstrate that isotope-edited infrared spectroscopy can distinguish aggregation modulators that integrate into the backbone structure of their interaction partner from those that do not. As an example for the latter case, the pro-inflammatory calcium binding protein S100A9 is shown not to incorporate into the b-sheets of A beta(42).
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| 2. |
- Baronio, Cesare M., et al.
(author)
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Insight into the internal structure of amyloid-β oligomers by isotope-edited Fourier transform infrared spectroscopy
- 2019
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 21:16, s. 8587-8597
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Journal article (peer-reviewed)abstract
- The internal structure of amyloid-β (Aβ) oligomers was investigated with isotope-edited Fourier transform infrared spectroscopy. Homo-oligomers of Aβ(40) and Aβ(42) were prepared from unlabeled and C-13, N-15-labeled monomeric Aβ and from mixtures of these. For the unlabeled peptides, two main bands were observed in (H2O)-H-2 at 1685 and 1622 cm(-1) for Aβ(40) and at 1685 and 1626 cm(-1) for Aβ(42). These band positions indicate that the number of strands per sheet is at least four. The obtained experimental amide I spectra were simulated using a number of structural models (antiparallel β-sheets, β-barrels and a dodecamer structure). According to experiments and calculations, the main C-13-band shifts down at increasing molar ratio of labeled peptides. This shift occurs when vibrational coupling becomes possible between C-13-amide groups in close-by strands. It is small, when intervening C-12-strands increase the distance between C-13-strands; it is large, when many neighboring strands are labeled. The shift depends on the internal structure of the peptides within the oligomers, i.e. on the building block that each peptide molecule contributes to the β-sheets of the oligomers. The shift is largest, when individual peptides contribute just a single strand surrounded by strands from other peptide molecules. It is smaller when each molecule forms two or three adjacent strands. As indicated by a comparison between experiment and computation, the number of adjacent β-strands per peptide molecule is two for Aβ(40) oligomers and two or more for Aβ(42) oligomers. Our results are well explained by regular, antiparallel β-sheets or β-barrels.
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| 3. |
- Baronio, Cesare M., 1987-, et al.
(author)
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Refining protein amide I spectrum simulations with simple yet effective electrostatic models for local wavenumbers and dipole derivative magnitudes
- 2024
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In: Physical Chemistry, Chemical Physics - PCCP. - 1463-9076 .- 1463-9084. ; 26:2, s. 1166-1181
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Journal article (peer-reviewed)abstract
- Analysis of the amide I band of proteins is probably the most wide-spread application of bioanalytical infrared spectroscopy. Although highly desirable for a more detailed structural interpretation, a quantitative description of this absorption band is still difficult. This work optimized several electrostatic models with the aim to reproduce the effect of the protein environment on the intrinsic wavenumber of a local amide I oscillator. We considered the main secondary structures – α-helices, parallel and antiparallel β-sheets – with a maximum of 21 amide groups. The models were based on the electric potential and/or the electric field component along the CO bond at up to four atoms in an amide group. They were bench-marked by comparison to Hessian matrices reconstructed from density functional theory calculations at the BPW91, 6-31G** level. The performance of the electrostatic models depended on the charge set used to calculate the electric field and potential. Gromos and DSSP charge sets, used in common force fields, were not optimal for the better performing models. A good compromise between performance and the stability of model parameters was achieved by a model that considered the electric field at the positions of the oxygen, nitrogen, and hydrogen atoms of the considered amide group. The model describes also some aspects of the local conformation effect and performs similar on its own as in combination with an explicit implementation of the local conformation effect. It is better than a combination of a local hydrogen bonding model with the local conformation effect. Even though the short-range hydrogen bonding model performs worse, it captures important aspects of the local wavenumber sensitivity to the molecular surroundings. We improved also the description of the coupling between local amide I oscillators by developing an electrostatic model for the dependency of the dipole derivative magnitude on the protein environment.
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| 4. |
- Baronio, Cesare M., et al.
(author)
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The amide I spectrum of parallel β-sheet proteins
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Other publication (other academic/artistic)abstract
- The amide I absorption of the polypeptide backbone has long been used to analyze the secondary structure of proteins. This approach has gained additional attention in the context of amyloid diseases where a particular focus is on the distinction between parallel and antiparallel β-sheets because these structures often discriminate between pre-fibrillar structures and fibrils. Some earlier infrared spectra with typical features of antiparallel β-sheets were interpreted as arising from the parallel β-sheets of fibrils. Therefore, the ability of infrared spectroscopy to distinguish between both types of β-sheets is debated. While it is established that regular, antiparallel β-sheets give rise to a high wavenumber band near 1690 cm-1, it is less clear whether or not this band may also occur for parallel β-sheets. Here we present and analyze the amide I spectra of two β-helix proteins, SV2 and Pent. The overall shape of the proteins is that of a cuboid which has parallel β-sheets on its four sides, which are connected by bends. The main features of their amide I spectrum are a band at 1665, and two bands between 1645 and 1628 cm-1. Both proteins exhibit also a weak component band near 1690 cm-1. Calculations of the amide I spectrum indicate that the absorption at high wavenumbers is not caused by the parallel β-sheets but by the bends between the β-strands. We therefore suggest to modify the interpretation of the amide I spectrum as follows: a high wavenumber band near 1690 cm-1 may be caused by other structures than antiparallel β-sheets. However, when the spectrum consists of only two distinct bands, one near 1690 cm-1 and one near 1630 cm-1, then an assignment to antiparallel β-sheets is consistent with the literature.
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| 5. |
- Baronio, Cesare M., et al.
(author)
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The Amide I Spectrum of Proteins—Optimization of Transition Dipole Coupling Parameters Using Density Functional Theory Calculations
- 2020
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 124:9, s. 1703-1714
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Journal article (peer-reviewed)abstract
- The amide I region of the infrared spectrum is related to the protein backbone conformation and can provide important structural information. However, the interpretation of the experimental results is hampered because the theoretical description of the amide I spectrum is still under development. Quantum mechanical calculations, for example, using density functional theory (DFT), can be used to study the amide I spectrum of small systems, but the high computational cost makes them inapplicable to proteins. Other approaches that solve the eigenvalues of the coupled amide I oscillator system are used instead. An important interaction to be considered is transition dipole coupling (TDC). Its calculation depends on the parameters of the transition dipole moment. This work aims to find the optimal parameters for TDC in three major secondary structures: α-helices, antiparallel β-sheets, and parallel β-sheets. The parameters were suggested through a comparison between DFT and TDC calculations. The comparison showed a good agreement for the spectral shape and for the wavenumbers of the normal modes for all secondary structures. The matching between the two methods improved when hydrogen bonding to the amide oxygen was considered. Optimal parameters for individual secondary structures were also suggested.
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| 6. |
- Carissimi, Guzmán, et al.
(author)
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On the Secondary Structure of Silk Fibroin Nanoparticles Obtained Using Ionic Liquids : An Infrared Spectroscopy Study
- 2020
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In: Polymers. - : MDPI AG. - 2073-4360. ; 12:6
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Journal article (peer-reviewed)abstract
- Silk fibroin from Bombyx mori caterpillar is an outstanding biocompatible polymer for the production of biomaterials. Its impressive combination of strength, flexibility, and degradability are related to the protein’s secondary structure, which may be altered during the manufacture of the biomaterial. The present study looks at the silk fibroin secondary structure during nanoparticle production using ionic liquids and high-power ultrasound using novel infrared spectroscopic approaches. The infrared spectrum of silk fibroin fibers shows that they are composed of 58% β-sheet, 9% turns, and 33% irregular and/or turn-like structures. When fibroin was dissolved in ionic liquids, its amide I band resembled that of soluble silk and no β-sheet absorption was detected. Silk fibroin nanoparticles regenerated from the ionic liquid solution exhibited an amide I band that resembled that of the silk fibers but had a reduced β-sheet content and a corresponding higher content of turns, suggesting an incomplete turn-to-sheet transition during the regeneration process. Both the analysis of the experimental infrared spectrum and spectrum calculations suggest a particular type of β-sheet structure that was involved in this deficiency, whereas the two other types of β-sheet structure found in silk fibroin fibers were readily formed.
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