Template-assisted filament growth by parallel stacking of tau
- 6 July 2004
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (28) , 10278-10283
- https://doi.org/10.1073/pnas.0401911101
Abstract
Tau filaments are found in >20 neurodegenerative diseases. Yet, because of their enormous molecular weights and poor tendency to form highly ordered 3D crystal lattices, they have evaded high-resolution structure determination. Here, we studied 25 derivatized tau mutants by using electron paramagnetic resonance and fluorescence spectroscopy to report structural details of tau filaments. Based on strong spin exchange and pyrene excimer formation of core residues, we find that individual tau proteins form single molecule layers along the fiber axis that perfectly stack on top of each other by in-register, parallel alignment of beta-strands. We suggest a model of filament growth wherein the existing filament serves as a template for the incoming, unfolded tau molecule, resulting in a new structured layer with maximized hydrogen-bonded contact surface and side-chain stacking.Keywords
This publication has 52 references indexed in Scilit:
- Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolutionJournal of Molecular Medicine, 2003
- Homotrimeric, β-Stranded Viral Adhesins and Tail ProteinsJournal of Bacteriology, 2003
- Dependence on solution conditions of aggregation and amyloid formation by an SH3 domainJournal of Molecular Biology, 2001
- Fibers of tau fragments, but not full length tau, exhibit a cross β‐structure: Implications for the formation of paired helical filamentsProtein Science, 2000
- Crystal structure of the glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus 1 1Edited by R. HuberJournal of Molecular Biology, 1999
- Structure of the KcsA Potassium Channel from Streptomyces lividans: A Site-Directed Spin Labeling Study of the Second Transmembrane SegmentBiochemistry, 1999
- Site-directed Spin Labeling Study of Subunit Interactions in the α-Crystallin Domain of Small Heat-shock ProteinsJournal of Biological Chemistry, 1999
- Polymerization of τ into Filaments in the Presence of Heparin: The Minimal Sequence Required for τ ‐ τ InteractionJournal of Neurochemistry, 1996
- Physical and chemical properties of purified tau factor and the role of tau in microtubule assemblyJournal of Molecular Biology, 1977
- Conformation of twisted β-pleated sheets in proteinsJournal of Molecular Biology, 1973