title: Microtubule-Binding R3 Fragment from Tau Self-Assembles into Giant Multistranded Amyloid Ribbons.
abstract: Tau protein and its fragments self-assemble into amyloid fibrils in the presence of polyanions, such as heparin. By combining microscopy, scattering, and spectroscopy techniques, we studied the aggregation of the 26-mer Tau-derived peptide alone, Tau(306-327), the third repeat fragment (R3) of the microtubule-binding domain. We show that: i) the sole Tau(306-327) can self-assemble into amyloid fibrils without the need of aggregation-promoting polyanions; ii) the resulting structures consist of surprisingly large, well-ordered 2D laminated flat ribbons, with a log-normal distribution of the lateral width, reaching the unprecedented lateral size of 350 nm and/or 45 individual protofilaments, that is, the largest amyloid laminated structures ever observed for Tau or any other amyloidogenic sequence. Our results provide insight into the molecular determinants of Tau aggregation and open new perspectives in the understanding of the assembly of amyloid fibrils and β-sheet-based biomaterials.
authors.affiliation: Department of Health Sciences and Technology, ETH Zürich, Schmelzbergstrasse 9, LFO E23, 8092 Zürich (Switzerland).
authors.forename: Jozef
authors.initials: J
authors.lastname: Adamcik
authors.affiliation: Department of Health Sciences and Technology, ETH Zürich, Schmelzbergstrasse 9, LFO E23, 8092 Zürich (Switzerland).
authors.forename: Antoni
authors.initials: A
authors.lastname: Sánchez-Ferrer
authors.affiliation: Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne (Switzerland).|Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, P.O. Box 5825 (Qatar).
authors.forename: Nadine
authors.initials: N
authors.lastname: Ait-Bouziad
authors.affiliation: ARC Training Centre for Biodevices, Faculty of Science Engineering and Technology, Swinburne University of Technology, John Street, Melbourne, Vic 3122 (Australia).|Manufacturing Flagship, CSIRO, Bayview Avenue, Clayton, Vic 3169 (Australia).
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Reynolds
authors.affiliation: Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne (Switzerland). hilal.lashuel@epfl.ch.|Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, P.O. Box 5825 (Qatar). hilal.lashuel@epfl.ch.
authors.forename: Hilal A
authors.initials: HA
authors.lastname: Lashuel
authors.affiliation: Department of Health Sciences and Technology, ETH Zürich, Schmelzbergstrasse 9, LFO E23, 8092 Zürich (Switzerland). raffaele.mezzenga@hest.ethz.ch.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Mezzenga
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D002942:Circular Dichroism; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D016875:tau Proteins / Q000737:chemistry*
chemical_list: D000682:Amyloid; D016875:tau Proteins
keywords: AFM; amyloids; peptide ribbons; self-assembly; statistical analysis