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Insight into the internal structure of amyloid-β oligomers by isotope-edited Fourier transform infrared spectroscopy
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.ORCID iD: 0000-0003-1399-748X
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.ORCID iD: 0000-0001-5784-7673
Number of Authors: 32019 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 21, no 16, p. 8587-8597Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 21, no 16, p. 8587-8597
National Category
Chemical Sciences Physical Sciences
Research subject
Biophysics
Identifiers
URN: urn:nbn:se:su:diva-170149DOI: 10.1039/c9cp00717bISI: 000465603200036PubMedID: 30964131OAI: oai:DiVA.org:su-170149DiVA, id: diva2:1331143
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2022-03-23Bibliographically approved
In thesis
1. Computational infrared spectroscopy: Calculation of the amide I absorption of proteins
Open this publication in new window or tab >>Computational infrared spectroscopy: Calculation of the amide I absorption of proteins
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Infrared spectroscopy is an important technique that allows to retrieve structural information from the analysis of absorption spectra. The main application of infrared spectroscopy within life science is the study of the amide I band, which is correlated with protein backbone conformation and, consequently, with the secondary structure of proteins. However, band assignment and interpretation of the infrared spectra is not straightforward.

Therefore, several simulation methods were developed to guide the interpretation of experimental amide I spectra. In this thesis, one of these methods is a normal mode analysis, which is based on the evaluation of the intrinsic vibration of the amide groups and the interactions between them. The calculation considers several effects: transition dipole coupling, nearest neighbor interaction, the local environment effect and the effect of hydrogen bond. From the normal mode analysis, it is possible to obtain the simulated infrared spectrum and the contribution of each amide group to a specific spectral range of the spectrum.

The aim of this thesis and of the included publications is to explain this approach, to improve it and to show its potential. Results from simulations were compared with experimental data for different proteins of interest: amyloid-β oligomers and β-helix proteins. Simulated and experimental infrared spectra showed similar bands. Simulations also provided additional conclusions: they confirmed the random mixing of amyloid-β peptides in oligomers; they suggested that amyloid-β peptides contribute at least two strands in the structure of the oligomers; they revealed that the high wavenumber band, typical of antiparallel β-sheets, can be caused by other secondary structures, but not by parallel β-sheets. In addition, to verify and to improve the accuracy of this approach, simulation results were also put in a direct comparison with results from density functional theory calculations. From this comparison, a new optimal set of parameters for the calculations is suggested.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2020. p. 63
Keywords
infrared spectroscopy, FTIR, simulation, calculation, amide I, transition dipole coupling, F matrix, protein, amyloid β, oligomers, β-helix
National Category
Chemical Sciences Physical Sciences
Research subject
Biophysics
Identifiers
urn:nbn:se:su:diva-179912 (URN)978-91-7911-074-1 (ISBN)978-91-7911-075-8 (ISBN)
Public defence
2020-04-29, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Available from: 2020-04-06 Created: 2020-03-13 Last updated: 2022-02-26Bibliographically approved

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Baronio, Cesare M.Baldassarre, MaurizioBarth, Andreas

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