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Not All ?-Sheets Are the Same: Amyloid Infrared Spectra, Transition Dipole Strengths, and Couplings Investigated by 2D IR Spectroscopy.

ABSTRACT: We report the transition dipole strengths and frequencies of the amyloid ?-sheet amide I mode for the aggregated proteins amyloid-?1-40, calcitonin, ?-synuclein, and glucagon. According to standard vibrational coupling models for proteins, the frequencies of canonical ?-sheets are set by their size and structural and environmental disorder, which determines the delocalization length of the vibrational excitons. The larger the delocalization the lower the frequency of the main infrared-allowed transition, A?. The models also predict an accompanying increase in transition dipole strength. For the proteins measured here, we find no correlation between transition dipole strengths and amyloid ?-sheet transition frequency. To understand this observation, we have extracted from the protein data bank crystal structures of amyloid peptides from which we calculate the amide I vibrational couplings, and we use these in a model ?-sheet Hamiltonian to simulate amyloid vibrational spectra. We find that the variations in amyloid ?-sheet structures (e.g., dihedral angles, interstrand distances, and orientations) create significant differences in the average values for interstrand and nearest neighbor couplings, and that those variations encompass the variation in measured A? frequencies. We also find that off-diagonal disorder about the average values explains the range of transition dipole strengths observed experimentally. Thus, we conclude that the lack of correlation between transition dipole-strength and frequency is caused by variations in amyloid ?-sheet structure. Taken together, these results indicate that the amide I frequency is very sensitive to amyloid ?-sheet structure, the ?-sheets of these 4 proteins are not identical, and the assumption that frequency of amyloids scales with ?-sheet size cannot be adopted without an accompanying measurement of transition dipole strengths.

SUBMITTER: Lomont JP

PROVIDER: S-EPMC5705941 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Not All β-Sheets Are the Same: Amyloid Infrared Spectra, Transition Dipole Strengths, and Couplings Investigated by 2D IR Spectroscopy.

Lomont Justin P JP Ostrander Joshua S JS Ho Jia-Jung JJ Petti Megan K MK Zanni Martin T MT

The journal of physical chemistry. B 20170919 38

We report the transition dipole strengths and frequencies of the amyloid β-sheet amide I mode for the aggregated proteins amyloid-β<sub>1-40</sub>, calcitonin, α-synuclein, and glucagon. According to standard vibrational coupling models for proteins, the frequencies of canonical β-sheets are set by their size and structural and environmental disorder, which determines the delocalization length of the vibrational excitons. The larger the delocalization the lower the frequency of the main infrared ...[more]

PMID: 28851219

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Project description:Infrared spectroscopy is playing an important role in the elucidation of amyloid fiber formation, but the coupling models that link spectra to structure are not well tested for parallel β-sheets. Using a synthetic macrocycle that enforces a two stranded parallel β-sheet conformation, we measured the lifetimes and frequency for six combinations of doubly (13)C═(18)O labeled amide I modes using 2D IR spectroscopy. The average vibrational lifetime of the isotope labeled residues was 550 fs. The frequencies of the labels ranged from 1585 to 1595 cm(-1), with the largest frequency shift occurring for in-register amino acids. The 2D IR spectra of the coupled isotope labels were calculated from molecular dynamics simulations of a series of macrocycle structures generated from replica exchange dynamics to fully sample the conformational distribution. The models used to simulate the spectra include through-space coupling, through-bond coupling, and local frequency shifts caused by environment electrostatics and hydrogen bonding. The calculated spectra predict the line widths and frequencies nearly quantitatively. Historically, the characteristic features of β-sheet infrared spectra have been attributed to through-space couplings such as transition dipole coupling. We find that frequency shifts of the local carbonyl groups due to nearest neighbor couplings and environmental factors are more important, while the through-space couplings dictate the spectral intensities. As a result, the characteristic absorption spectra empirically used for decades to assign parallel β-sheet secondary structure arises because of a redistribution of oscillator strength, but the through-space couplings do not themselves dramatically alter the frequency distribution of eigenstates much more than already exists in random coil structures. Moreover, solvent exposed residues have amide I bands with >20 cm(-1) line width. Narrower line widths indicate that the amide I backbone is solvent protected inside the macrocycle. This work provides calculated and experimentally verified couplings for parallel β-sheets that can be used in structure-based models to simulate and interpret the infrared spectra of β-sheet containing proteins and protein assemblies, such as amyloid fibers.

Dataset Information

Not All ?-Sheets Are the Same: Amyloid Infrared Spectra, Transition Dipole Strengths, and Couplings Investigated by 2D IR Spectroscopy.

Publications

Not All β-Sheets Are the Same: Amyloid Infrared Spectra, Transition Dipole Strengths, and Couplings Investigated by 2D IR Spectroscopy.

Similar Datasets

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