Dataset Information

Two-dimensional infrared spectra of isotopically diluted amyloid fibrils from Abeta40.

ABSTRACT: The 2D IR spectra of the amide-I vibrations of amyloid fibrils from Abeta40 were obtained. The matured fibrils formed from strands having isotopic substitution by (13)C (18)O at Gly-38, Gly-33, Gly-29, or Ala-21 show vibrational exciton spectra having reduced dimensionality. Indeed, linear chain excitons of amide units are seen, for which the interamide vibrational coupling is measured in fibrils grown from 50% and 5% mixtures of labeled and unlabeled strands. The data prove that the 1D excitons are formed from parallel in-register sheets. The coupling constants show that for each of the indicated residues the amide carbonyls in the chains are separated by 0.5 +/- 0.05 nm. The isotope replacement of Gly-25 does not reveal linear excitons, consistent with the region of the strand having a different structure distribution. The vibrational frequencies of the amide-I modes, freed from effects of amide vibrational excitation exchange by 5% dilution experiments, point to there being a component of an electric field along the fibril axis that increases through the sequence Gly-38, Gly-33, Gly-29. The field is dominated by side chains of neighboring residues.

SUBMITTER: Kim YS

PROVIDER: S-EPMC2409414 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Two-dimensional infrared spectra of isotopically diluted amyloid fibrils from Abeta40.

Kim Yung Sam YS Liu Liu L Axelsen Paul H PH Hochstrasser Robin M RM

Proceedings of the National Academy of Sciences of the United States of America 20080522 22

The 2D IR spectra of the amide-I vibrations of amyloid fibrils from Abeta40 were obtained. The matured fibrils formed from strands having isotopic substitution by (13)C (18)O at Gly-38, Gly-33, Gly-29, or Ala-21 show vibrational exciton spectra having reduced dimensionality. Indeed, linear chain excitons of amide units are seen, for which the interamide vibrational coupling is measured in fibrils grown from 50% and 5% mixtures of labeled and unlabeled strands. The data prove that the 1D excitons ...[more]

PMID: 18499799

Similar Datasets

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

Two-dimensional infrared spectra of isotopically diluted amyloid fibrils from Abeta40.

Publications

Two-dimensional infrared spectra of isotopically diluted amyloid fibrils from Abeta40.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets