Microtubule‐Binding R3 Fragment from Tau Self‐Assembles into Giant Multistranded Amyloid Ribbons |
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| Authors: | Dr Jozef Adamcik Dr Antoni Sánchez‐Ferrer Nadine Ait‐Bouziad Dr Nicholas P Reynolds Prof?Dr Hilal A Lashuel Prof?Dr Raffaele Mezzenga |
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| Institution: | 1. Department of Health Sciences and Technology, ETH Zürich, Schmelzbergstrasse 9, LFO E23, 8092 Zürich (Switzerland);2. Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne (Switzerland);3. Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, P.O. Box 5825 (Qatar);4. ARC Training Centre for Biodevices, Faculty of Science Engineering and Technology, Swinburne University of Technology, John Street, Melbourne, Vic 3122 (Australia);5. Manufacturing Flagship, CSIRO, Bayview Avenue, Clayton, Vic 3169 (Australia) |
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| 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, Tau306–327, the third repeat fragment (R3) of the microtubule‐binding domain. We show that: i) the sole Tau306–327 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. |
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| Keywords: | AFM amyloids peptide ribbons self‐assembly statistical analysis |
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