TY - JOUR
T1 - An Additive-Free Model for Tau Self-Assembly
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.
N1 - Publisher Copyright:
© 2023. Springer Science+Business Media, LLC, part of Springer Nature.
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
UR - http://www.scopus.com/inward/record.url?scp=85141005311&partnerID=8YFLogxK
U2 - 10.1007/978-1-0716-2597-2_12
DO - 10.1007/978-1-0716-2597-2_12
M3 - Article
C2 - 36310203
AN - SCOPUS:85141005311
VL - 2551
SP - 163
EP - 188
JO - Methods in molecular biology (Clifton, N.J.)
JF - Methods in molecular biology (Clifton, N.J.)
SN - 1940-6029
ER -