STI1 domain dynamically engages transient helices in disordered regions to drive self-association and phase separation of yeast ubiquilin Dsk2
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 14, 2025
Ubiquitin-binding
shuttle
proteins
are
important
components
of
stress-induced
biomolecular
condensates
in
cells.
Yeast
Dsk2
scaffolds
proteasome-containing
via
multivalent
interactions
with
proteasomes
and
ubiquitinated
substrates
under
azide-induced
mitochondrial
stress
or
extended
growth
conditions.
However,
the
molecular
mechanisms
underlying
how
these
work
unknown.
Here,
we
identify
that
middle
chaperone-binding
STI1
domain
is
main
driver
self-association
phase
separation
vitro.
On
a
level,
find
interacts
three
transient
amphipathic
helices
within
intrinsically-disordered
regions
Dsk2.
Removal
either
significantly
reduces
propensity
for
to
separate.
In
vivo,
removal
has
opposite
effect,
resulting
an
increase
due
accumulation
polyubiquitinated
substrates.
Modeling
STI1-helix
reveals
binding
mode
reminiscent
between
chaperone
STI1/DP2
domains
client
containing
transmembrane
helices.
Our
findings
support
model
whereby
condensate
formation
can
be
replaced
by
STI1-client
downstream
other
protein
quality
control
outcomes.
Language: Английский
Neurotropic Viruses as Acute and Insidious Drivers of Aging
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(4), P. 514 - 514
Published: April 1, 2025
Aging
is
the
result
of
various
compounding
stresses
that
gradually
overcome
homeostatic
regulation
cell,
resulting
in
irreversible
damage.
This
manifests
as
many
acute
and
chronic
conditions,
most
common
which
are
neurodegeneration
dementia.
Epidemiological
studies
have
shown
significant,
strong
correlations
between
viral
infection
neurodegenerative
diseases.
review
overlays
characteristics
pathogenesis
with
hallmarks
aging
to
discuss
how
active
latent
viruses
contribute
aging.
Through
our
contextualization
myriad
basic
science
papers,
we
offer
explanations
for
premature
via
induction
stress
response
pathways.
Viruses
induce
stresses:
dysregulated
homeostasis
by
exogenous
proteins
overwhelmed
protein
quality
control
mechanisms,
DNA
damage
through
direct
integration
epigenetic
manipulation,
immune-mediated
oxidative
immune
exhaustion,
general
energy
theft
amplified
an
system.
Overall,
this
highlights
long-term
importance
vaccines
antivirals
addition
their
benefits.
Language: Английский