Comparison of Alzheimer Aβ(1–40) and Aβ(1–42) amyloid fibrils reveals similar protofilament structures
- Matthias Schmidta,b,c,
- Carsten Sachsea,b,1,
- Walter Richterd,
- Chen Xua,
- Marcus Fändrichb and
- Nikolaus Grigorieffa,c,2
- aRosenstiel Basic Medical Sciences Research Center and
- cHoward Hughes Medical Institute, Brandeis University, MS 029, Waltham, MA 02454-9110;
- bMax-Planck Research Unit for Enzymology of Protein Folding and Martin-Luther University Halle-Wittenberg, Weinbergweg 22, 01620 Halle (Saale), Germany; and
- dElektronenmikroskopisches Zentrum, Friedrich-Schiller-Universität Jena, Ziegelmühlenweg 1, 07740 Jena, Germany
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Edited by David Baker, University of Washington, Seattle, WA, and approved September 16, 2009 (received for review May 6, 2009)
Abstract
We performed mass-per-length (MPL) measurements and electron cryomicroscopy (cryo-EM) with 3D reconstruction on an Aβ(1–42) amyloid fibril morphology formed under physiological pH conditions. The data show that the examined Aβ(1–42) fibril morphology has only one protofilament, although two protofilaments were observed with a previously studied Aβ(1–40) fibril. The latter fibril was resolved at 8 Å resolution showing pairs of β-sheets at the cores of the two protofilaments making up a fibril. Detailed comparison of the Aβ(1–42) and Aβ(1–40) fibril structures reveals that they share an axial twofold symmetry and a similar protofilament structure. Furthermore, the MPL data indicate that the protofilaments of the examined Aβ(1–40) and Aβ(1–42) fibrils have the same number of Aβ molecules per cross-β repeat. Based on this data and the previously studied Aβ(1–40) fibril structure, we describe a model for the arrangement of peptides within the Aβ(1–42) fibril.
Footnotes
- 2To whom correspondence may be addressed. E-mail: fandrich{at}enzyme-halle.mpg.de or niko{at}brandeis.edu
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Author contributions: M.F. and N.G. designed research; M.S., C.S., W.R., and C.X. performed research; W.R. contributed new reagents/analytic tools; M.S., C.S., M.F., and N.G. analyzed data; and M.S., M.F., and N.G. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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Data deposition: Density maps have been deposited in the Macromolecular Structure Database of the European Bioinformatics Institute {accession codes EMD-1649 [twofold symmetrized Aβ(1–42) fibrils] and EMD-1650 [13-nm Aβ(1–40) fibrils]}.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0905007106/DCSupplemental.
