Report

Fibril structure of amyloid-β(1–42) by cryo–electron microscopy

See allHide authors and affiliations

Science  06 Oct 2017:
Vol. 358, Issue 6359, pp. 116-119
DOI: 10.1126/science.aao2825
  • Fig. 1 Aβ(1–42) fibril structure.

    (A) 3D reconstruction from cryo-EM images showing density of two protofilaments (brown and blue) and the clear separation of the β strands. (B) Atomic model of the fibril with parallel cross-β structure. (C and D) Tilted views of the cross section of the EM density and the backbone model.

  • Fig. 2 Atomic model and superimposed EM density of the fibril cross section.

    (A) Two subunits, one from each protofilament, are shown (blue and brown), together with the masked EM density map (at a contour level of 1.5 σ; additional contour levels of 1 σ and 2 σ are shown in fig. S4). (B) Detailed view of the interactions between the N and C terminus and the side chain of Lys28 (at a contour level of 1 σ). (C) Side view of the same two opposing subunits showing the relative orientation of the nonplanar subunits. The large peripheral cross-β sheets are tilted by 10° with respect to the plane perpendicular to the fibril axis.

  • Fig. 3 NMR and x-ray diffraction experiments.

    (A) 2D proton-driven spin diffusion (PDSD) spectrum of fibrillar Aβ(1–42). The spectrum was recorded at a magnetic field strength of 18.8 T, corresponding to a proton Larmor frequency of 800 MHz, a sample temperature of T = 0 ± 5°C, and a spinning speed of 12.5 kHz. For homonuclear 13C/13C mixing, PDSD with a mixing time of 20 ms was used. A squared and shifted sine bell function was used for apodization (shift of 0.3·π). (B) Secondary chemical shifts calculated from assigned resonance shifts and random coil values predicting β-strand regions [difference exceeds –2 parts per million (ppm)] (dark blue). For Gly residues, only the Cα secondary chemical shifts are plotted. Additionally, β strands calculated by the program TALOS-N and β sheets from the cryo-EM derived atomic model are displayed (assigned by the programs DSSP and Stride). (C) X-ray diffraction image of unoriented Aβ(1–42) fibrils. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.

  • Fig. 4 Details of the Aβ(1–42) fibril architecture.

    (A) Side view of the atomic model showing the staggered arrangement of the nonplanar subunits. (B) Surface representation of a fragment of the atomic fibril model. Surface is colored according to hydrophobicity (Kyte-Doolittle scale) [gradient from brown (hydrophobic, 4.5) to white (neutral, 0.0)]. (C and D) View of the “ridge” (C) and “groove” (D) fibril ends. Only the contact surfaces of the subunits with the respective capping monomer [i+3 in (C) and i-4 in (D), shown as ribbons] are colored [color coding according to layer number; see (A)].

Supplementary Materials

  • Fibril structure of amyloid-β(1-42) by cryoelectron microscopy

    Lothar Gremer, Daniel Schölzel, Carla Schenk, Elke Reinartz, Jörg Labahn, Raimond B. G. Ravelli, Markus Tusche, Carmen Lopez-Iglesias, Wolfgang Hoyer, Henrike Heise, Dieter Willbold, Gunnar F. Schröder

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

    Download Supplement
    • Materials and Methods
    • Figs. S1 to S13
    • Tables S1 to S7
    • References

    Images, Video, and Other Media

    Movie S1
    Showing the density map of the fibril (corresponding to Fig. 1A).
    Movie S2
    Showing the ridge end of the fibril (corresponding to Fig. 4C).
    Movie S3
    Showing the groove end of the fibril (corresponding to Fig. 4D).

Navigate This Article