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Microtubule‐Binding R3 Fragment from Tau Self‐Assembles into Giant Multistranded Amyloid Ribbons
Author(s) -
Adamcik Jozef,
SánchezFerrer Antoni,
AitBouziad Nadine,
Reynolds Nicholas P.,
Lashuel Hilal A.,
Mezzenga Raffaele
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201508968
Subject(s) - fibril , microtubule , amyloid fibril , amyloid (mycology) , chemistry , biophysics , peptide , crystallography , amyloid β , sequence (biology) , self assembly , biochemistry , biology , microbiology and biotechnology , medicine , inorganic chemistry , disease , pathology , organic chemistry
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.