Structure of amyloid fibrils
Knowledge about the fibril structure is a prerequisite to the understanding of the
forces and biophysical principles stabilising these states as well as for structure-
based design methods to interfere with their formation. One method used by our
lab for studying amyloid fibrils is cryo electron microscopy, a technique which is
specifically of advantage when dealing with species of high molecular weight
and symmetry, such as amyloid fibrils. Using this technique have investigated
the together with the group of Niko Grigorieff (Brandeis University, U.S.A.)
structure of a mature amyloid fibril formed from the Alzheimer's Aβ(1-40)
peptide. Other techniqes include Fourier-transform infrared (FTIR), circular
dichroism (CD) and fluorescence spectroscopy.
Selected references:
●
Sachse C, Grigorieff N, Fändrich M.
Nanoscale Flexibility parameters of Alzheimer amyloid fibrils determined using electron cryo-
microscopy.
Angewandte Chemie Int. Ed. 2010, 49, 1321-1323
●
Schmidt M, Sachse C, Richter W, Xu C, Fändrich M, Grigorieff N
Comparison of Alzheimer Aß(1-40) and Aß(1-42) amyloid fibrils reveals similar protofilament structures.
Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 19813-19818
●
Meinhardt J, Sachse C, Hortschansky P, Grigorieff N, Fändrich M.
Aß(1-40) fibril polymorphism implies diverse interaction patterns in amyloid fibrils.
J. Mol. Biol. 2009, 386, 869–877
●
Sachse C, Fändrich M, Grigorieff N.
Paired ß-sheet structure of an Aß(1-40) amyloid fibril revealed by electron microscopy.
Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 7462-6.
●
Zandomeneghi G, Krebs MRH, McCammon MG and Fändrich M.
FTIR reveals structural differences between native beta-sheet proteins and amyloid fibrils.
Protein Sci. 2004, 13, 3314-3321.
