Microtubule-Binding R3 Fragment from Tau Self-Assembles into Giant Multistranded Amyloid Ribbons

Jozef Adamcik, Antoni Sánchez-Ferrer, Nadine Ait-Bouziad, Nicholas P. Reynolds, Hilal A. Lashuel, Raffaele Mezzenga

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)618-622
Number of pages5
JournalAngewandte Chemie - International Edition
Volume55
Issue number2
DOIs
Publication statusPublished - 11 Jan 2016

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Keywords

  • AFM
  • amyloids
  • peptide ribbons
  • self-assembly
  • statistical analysis

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

Cite this

Adamcik, J., Sánchez-Ferrer, A., Ait-Bouziad, N., Reynolds, N. P., Lashuel, H. A., & Mezzenga, R. (2016). Microtubule-Binding R3 Fragment from Tau Self-Assembles into Giant Multistranded Amyloid Ribbons. Angewandte Chemie - International Edition, 55(2), 618-622. https://doi.org/10.1002/anie.201508968