Intracellular inclusions of the the versatile
RNA/DNA binding protein TDP-43 are
commonly found in cases of AD, as well as
certain forms of ALS and frontotemporal
lobar degeneration. Previous studies
have shown that zinc ions bind to and
induce the aggregation of amyloid-beta
Discover the
molecular
mechanism of
zinc-induced
protein
aggregation
3
Molecular
interactions
studied
Target: TDP-43
Ligand: zinc
Method
nanoDSF using
Prometheus
Learn more
in AD development. Recently, it was
proposed that zinc can also induce TDP-43
aggregation in cells, though the molecular
mechanism has yet to be studied.
Researchers sought to examine
the involvement of zinc ions in the
mechanism of TDP-43 aggregation.
More specifically, they looked at the
interaction of zinc ions with the two RNA-
recognition motifs of TDP-43, and the
impact on the tertiary structure of the
protein.
Using a combination of ITC, MS, and
nanoDSF, this paper showed that zinc
binds directly to RNA-recognition domains
of TDP-43. Upon binding, zinc induces
tertiary structure changes that decrease
the thermostability of the RNA-recognition
domains and induce aggregation.
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