An Additive-Free Model for Tau Self-Assembly

Youssra K. Al-Hilaly; Karen E. Marshall; Liisa Lutter; Luca Biasetti; Kurtis Mengham; Charles R. Harrington; Wei Feng Xue; Claude M. Wischik; Louise C. Serpell

doi:10.1007/978-1-0716-2597-2_12

An Additive-Free Model for Tau Self-Assembly

Youssra K. Al-Hilaly, Karen E. Marshall, Liisa Lutter, Luca Biasetti, Kurtis Mengham, Charles R. Harrington, Wei Feng Xue, Claude M. Wischik, Louise C. Serpell

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Tau is a natively unfolded protein that contributes to the stability of microtubules. Under pathological conditions such as Alzheimer's disease (AD), tau protein misfolds and self-assembles to form paired helical filaments (PHFs) and straight filaments (SFs). Full-length tau protein assembles poorly and its self-assembly is enhanced with polyanions such as heparin and RNA in vitro, but a role for heparin or other polyanions in vivo remains unclear. Recently, a truncated form of tau (297-391) has been shown to self-assemble in the absence of additives which provides an alternative in vitro PHF model system. Here we describe methods to prepare in vitro PHFs and SFs from tau (297-391) named dGAE. We also discuss the range of biophysical/biochemical techniques used to monitor tau filament assembly and structure.

Original language	English
Pages (from-to)	163-188
Number of pages	26
Journal	Methods in molecular biology (Clifton, N.J.)
Volume	2551
Early online date	31 Oct 2022
DOIs	https://doi.org/10.1007/978-1-0716-2597-2_12
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
© 2023. Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

Atomic force microscopy
Circular dichroism
Cross-beta
Electron microscopy
Paired helical filament
Self-assembly
Tau
Thioflavin S fluorescence
Tyrosine fluorescence
X-ray fibre diffraction

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10.1007/978-1-0716-2597-2_12

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title = "An Additive-Free Model for Tau Self-Assembly",

abstract = "Tau is a natively unfolded protein that contributes to the stability of microtubules. Under pathological conditions such as Alzheimer's disease (AD), tau protein misfolds and self-assembles to form paired helical filaments (PHFs) and straight filaments (SFs). Full-length tau protein assembles poorly and its self-assembly is enhanced with polyanions such as heparin and RNA in vitro, but a role for heparin or other polyanions in vivo remains unclear. Recently, a truncated form of tau (297-391) has been shown to self-assemble in the absence of additives which provides an alternative in vitro PHF model system. Here we describe methods to prepare in vitro PHFs and SFs from tau (297-391) named dGAE. We also discuss the range of biophysical/biochemical techniques used to monitor tau filament assembly and structure.",

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AU - Al-Hilaly, Youssra K.

AU - Marshall, Karen E.

AU - Lutter, Liisa

AU - Biasetti, Luca

AU - Mengham, Kurtis

AU - Harrington, Charles R.

AU - Xue, Wei Feng

AU - Wischik, Claude M.

AU - Serpell, Louise C.

PY - 2023

Y1 - 2023

N2 - Tau is a natively unfolded protein that contributes to the stability of microtubules. Under pathological conditions such as Alzheimer's disease (AD), tau protein misfolds and self-assembles to form paired helical filaments (PHFs) and straight filaments (SFs). Full-length tau protein assembles poorly and its self-assembly is enhanced with polyanions such as heparin and RNA in vitro, but a role for heparin or other polyanions in vivo remains unclear. Recently, a truncated form of tau (297-391) has been shown to self-assemble in the absence of additives which provides an alternative in vitro PHF model system. Here we describe methods to prepare in vitro PHFs and SFs from tau (297-391) named dGAE. We also discuss the range of biophysical/biochemical techniques used to monitor tau filament assembly and structure.

AB - Tau is a natively unfolded protein that contributes to the stability of microtubules. Under pathological conditions such as Alzheimer's disease (AD), tau protein misfolds and self-assembles to form paired helical filaments (PHFs) and straight filaments (SFs). Full-length tau protein assembles poorly and its self-assembly is enhanced with polyanions such as heparin and RNA in vitro, but a role for heparin or other polyanions in vivo remains unclear. Recently, a truncated form of tau (297-391) has been shown to self-assemble in the absence of additives which provides an alternative in vitro PHF model system. Here we describe methods to prepare in vitro PHFs and SFs from tau (297-391) named dGAE. We also discuss the range of biophysical/biochemical techniques used to monitor tau filament assembly and structure.

KW - Atomic force microscopy

KW - Circular dichroism

KW - Cross-beta

KW - Electron microscopy

KW - Paired helical filament

KW - Self-assembly

KW - Tau

KW - Thioflavin S fluorescence

KW - Tyrosine fluorescence

KW - X-ray fibre diffraction

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SN - 1940-6029

VL - 2551

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JO - Methods in molecular biology (Clifton, N.J.)

JF - Methods in molecular biology (Clifton, N.J.)

ER -

An Additive-Free Model for Tau Self-Assembly

Abstract

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Keywords

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