Sachse C, Fändrich M, Grigorieff N.
Paired beta-sheet structure of an Abeta(1-40) amyloid fibril revealed by electron microscopy.
Proc Natl Acad Sci U S A. 2008 May 27;105(21):7462-6.
PubMed.
Despite many years of efforts in trying to solve the structure of Aβ fibrils, a high-resolution structure of the fibrils is still not available. To this end, one of the obstacles is heterogeneity in the morphology of Aβ fibrils. In this interesting study, the authors carefully selected fibrils with similar morphologies based on their width and helical twists. With the help of advanced image-processing methods, Sachse et al. obtained an ~8 angstrom cryo-EM image of the Aβ fibril. Although at this resolution it is impossible to obtain the atomic structure of the fibrils, the cryo-EM image reveals important features. For example, the fibril consists of two protofilaments. Each protofilament exhibits a local twofold symmetry, suggesting that pairs of β-sheets are formed from equivalent parts of two Aβ peptides. The cross-β pairing of two β-sheets in each protofilament resembles steric-zipper-like structures. It is interesting that the core of the protofibril displays a zigzag shape, suggesting multiple steric-zippers. A high-resolution model of Aβ fibril might be possible by molecular modeling and fitting of the cryo-EM image.
Comments
University of North Carolina
Despite many years of efforts in trying to solve the structure of Aβ fibrils, a high-resolution structure of the fibrils is still not available. To this end, one of the obstacles is heterogeneity in the morphology of Aβ fibrils. In this interesting study, the authors carefully selected fibrils with similar morphologies based on their width and helical twists. With the help of advanced image-processing methods, Sachse et al. obtained an ~8 angstrom cryo-EM image of the Aβ fibril. Although at this resolution it is impossible to obtain the atomic structure of the fibrils, the cryo-EM image reveals important features. For example, the fibril consists of two protofilaments. Each protofilament exhibits a local twofold symmetry, suggesting that pairs of β-sheets are formed from equivalent parts of two Aβ peptides. The cross-β pairing of two β-sheets in each protofilament resembles steric-zipper-like structures. It is interesting that the core of the protofibril displays a zigzag shape, suggesting multiple steric-zippers. A high-resolution model of Aβ fibril might be possible by molecular modeling and fitting of the cryo-EM image.
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