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Fibers of tau fragments, but not full length tau, exhibit a cross β‐structure: Implications for the formation of paired helical filaments
Author(s) -
Giannetti A. M.,
Lindwall G.,
Kohlstaedt L. A.,
Chau M.F.,
Radeke M. J.,
Feinstein S. C.
Publication year - 2000
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.9.12.2427
Subject(s) - fiber diffraction , electron microscope , fibril , biophysics , tau protein , chemistry , fiber , morphology (biology) , crystallography , nucleation , folding (dsp implementation) , alzheimer's disease , x ray crystallography , diffraction , biology , physics , pathology , genetics , disease , optics , medicine , organic chemistry , electrical engineering , engineering
We have used X‐ray fiber diffraction to probe the structure of fibers of tau and tau fragments. Fibers of fragments from the microtubule binding domain had a cross β‐structure that closely resembles that reported both for neurofibrillary tangles found in Alzheimer's disease brain and for fibrous lesions from other protein folding diseases. In contrast, fibers of full‐length tau had a different, more complex structure. Despite major differences at the molecular level, all fiber types exhibited very similar morphology by electron microscopy. These results have a number of implications for understanding the etiology of Alzheimer's and other tauopathic diseases. The morphology of the peptide fibers suggests that the region in tau corresponding to the peptides plays a critical role in the nucleation of fiber assembly. The dramatically different structure of the full length tau fibers suggests that some region in tau has enough inherent structure to interfere with the formation of cross β‐fibers. Additionally, the similar appearance by electron microscopy of fibrils with varying molecular structure suggests that different molecular arrangements may exist in other samples of fibers formed from tau.