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ATP enhances at low concentrations but dissolves at high concentrations liquid-liquid phase separation (LLPS) of ALS/FTD-causing FUS.

Abstract：

:ATP is the universal energy currency but mysteriously its cellular concentration is much higher than that needed for providing energy. Recently ATP was decoded to act as a hydrotrope to dissolve liquid-liquid phase separation (LLPS) of FUS whose aggregation leads to ALS/FTD. By DIC microscopy and NMR, here we characterized the effect of ATP on LLPS of FUS and its N-/C-terminal domains. Very unexpectedly, we found that like nucleic acids, ATP enhances LLPS of FUS at low but dissolves at high concentrations. Intriguingly, ATP monotonically dissolves LLPS of NTD, while it induces LLPS of CTD at low but dissolves at high concentrations. Our study reveals for the first time that ATP can enhance LLPS most likely by behaving as a bivalent binder. Most importantly, our results imply that age-dependent reduction of ATP concentrations may not only result in decreasing its capacity in preventing protein aggregation, but also in enhancing aggregation.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kang J,Lim L,Song J

doi

10.1016/j.bbrc.2018.09.014

subject

Has Abstract

pub_date

2018-10-02 00:00:00

pages

545-551

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)31925-9

journal_volume

504

pub_type

杂志文章

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