Two-dimensional infrared spectra of isotopically diluted amyloid fibrils from Abeta40 - PubMed (original) (raw)

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

Yung Sam Kim et al. Proc Natl Acad Sci U S A. 2008.

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Fig. 1.

Diagrams of Aβ40 fibrils. (A) A cross section of two laterally displaced molecular layers of the Aβ40 fibril according to Petkova et al. (6). Residues 9–40 are shown. (B) Idealized structure of a portion of the parallel β-sheet. The strands are indicated by s, and the residue number in a given strand is indicated by n. The asterisk denotes the carbonyl group of a 13Cformula image18O doubly labeled amide group. Dotted lines represent hydrogen bonds.

Fig. 2.

Fig. 2.

Linear and 2D IR spectra of Aβ40 doubly labeled with 13Cformula image18O at Gly-38 (G38*) and a 1:1 mixture of G38* and unlabeled Aβ40 (G38*/G38) at different maturation times. (A–C) Linear IR spectra and 2D IR spectra at T = 0 of G38* at maturation times of 6 days (A), 12 days (B), and 19 days (C). (D–F) Linear IR spectra and 2D IR spectra at T = 0 of G38*/G38 at maturation times of 6 days (D), 12 days (E), and 19 days (F). The Inset in each 2D spectrum is an enlarged and four-times-intensified view of the area enclosed by the outlined region. The dotted circles in the linear spectra of A–C highlight the isotope-labeled amide-I transition regions. The magnitude of each 2D spectrum was scaled to have the same difference of maximum and minimum values.

Fig. 3.

Fig. 3.

Experimental and simulated traces of the Aβ40 fibril 2D IR spectra at T = 0. (A–C) Traces of the 2D IR signal along a line ωt = ωτ + 2 cm−1 for A21* (solid) and A21*/A21 (dotted) (A), G33* (solid) and G33*/G33 (dotted) (B), and G38* (solid) and G38*/G38 (dotted) (C). (D) Simulated traces of the 2D IR spectra of fibrils formed from a 100% (solid), 50% (dotted), and 5% (dashed) G33-labeled peptide. The thick vertical line in D represents the frequency νo (defined in the text) of the isotope-labeled amide-I transition in the absence of any coupling. The coupling constant for the simulation of G33 (D) is α = −9.5 cm−1.

Fig. 4.

Fig. 4.

2D IR spectra of fibrils of G25* (13Cformula image18O labeled at Gly-25) (A) and G29* (13Cformula image18O labeled at Gly-29) (B) at T = 0 after 70 days of maturation. In each spectrum the white area corresponds to a flat top off-scale signal. The contours begin at 25% of the peak signals. The Insets are enlarged and 10-times-intensified (A) and two-times-intensified (B) views of the marked areas.

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