Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Oct. 9, 2024
Parkinson's
disease
(PD)
and
Dementia
with
Lewy
Bodies
(DLB)
are
neurodegenerative
disorders
characterized
by
the
accumulation
of
α-synuclein
aggregates.
forms
droplets
via
liquid-liquid
phase
separation
(LLPS),
followed
liquid-solid
(LSPS)
to
form
amyloids,
how
this
process
is
physiologically-regulated
remains
unclear.
β-synuclein
colocalizes
in
presynaptic
terminals.
Here,
we
report
that
partitions
into
condensates
promotes
LLPS,
slows
down
LSPS
α-synuclein,
while
disease-associated
mutations
lose
these
capacities.
Exogenous
improves
movement
defects
prolongs
lifespan
an
α-synuclein-expressing
NL5901
Caenorhabditis
elegans
strain,
mutants
aggravate
symptoms.
Decapeptides
targeted
at
α-/β-synuclein
interaction
sites
rationally
designed,
which
suppress
rescue
defects,
prolong
C.
NL5901.
Together,
unveil
a
Yin-Yang
balance
between
α-
underlying
normal
states
PD
DLB
therapeutical
potentials.
Nature Chemistry,
Journal Year:
2024,
Volume and Issue:
16(7), P. 1073 - 1082
Published: Feb. 21, 2024
Endogenous
biomolecular
condensates,
composed
of
a
multitude
proteins
and
RNAs,
can
organize
into
multiphasic
structures
with
compositionally
distinct
phases.
This
organization
is
generally
understood
to
be
critical
for
facilitating
their
proper
biological
function.
However,
the
biophysical
principles
driving
multiphase
formation
are
not
completely
understood.
Here
we
use
in
vivo
condensate
reconstitution
experiments
coarse-grained
molecular
simulations
investigate
how
oligomerization
sequence
interactions
modulate
condensates.
We
demonstrate
that
increasing
state
an
intrinsically
disordered
protein
results
enhanced
immiscibility
formation.
Interestingly,
find
tunes
miscibility
asymmetric
manner,
effect
being
more
pronounced
when
protein,
exhibiting
stronger
homotypic
interactions,
oligomerized.
Our
findings
suggest
flexible
mechanism
cells
exploit
tune
internal
condensates
associated
functions.
The EMBO Journal,
Journal Year:
2024,
Volume and Issue:
43(9), P. 1898 - 1918
Published: April 2, 2024
Abstract
We
introduce
MolPhase,
an
advanced
algorithm
for
predicting
protein
phase
separation
(PS)
behavior
that
improves
accuracy
and
reliability
by
utilizing
diverse
physicochemical
features
extensive
experimental
datasets.
MolPhase
applies
a
user-friendly
interface
to
compare
distinct
biophysical
side-by-side
along
sequences.
By
additional
comparison
with
structural
predictions,
enables
efficient
predictions
of
new
phase-separating
proteins
guides
hypothesis
generation
design.
Key
contributing
factors
underlying
include
electrostatic
pi-interactions,
disorder,
prion-like
domains.
As
example,
finds
phytobacterial
type
III
effectors
(T3Es)
are
highly
prone
homotypic
PS,
which
was
experimentally
validated
in
vitro
biochemically
vivo
plants,
mimicking
their
injection
accumulation
the
host
during
microbial
infection.
The
characteristics
T3Es
dictate
patterns
association
multivalent
interactions,
influencing
material
properties
droplets
based
on
surrounding
microenvironment
or
vitro.
Robust
integration
MolPhase’s
effective
prediction
validation
exhibit
potential
evaluate
explore
how
biomolecule
PS
functions
biological
systems.
The Plant Cell,
Journal Year:
2023,
Volume and Issue:
35(9), P. 3173 - 3186
Published: March 5, 2023
Abstract
This
review
highlights
recent
literature
on
biomolecular
condensates
in
plant
development
and
discusses
challenges
for
fully
dissecting
their
functional
roles.
Plant
developmental
biology
has
been
inundated
with
descriptive
examples
of
condensate
formation,
but
it
is
only
recently
that
mechanistic
understanding
forthcoming.
Here,
we
discuss
potential
roles
play
at
different
stages
the
life
cycle.
We
group
these
based
putative
molecular
functions,
including
sequestering
interacting
components,
enhancing
dwell
time,
cytoplasmic
biophysical
properties
response
to
environmental
change.
explore
how
mechanisms
could
modulate
inputs
opportunities
further
research
into
deciphering
better
understand
diverse
exert
life.
Nucleus,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: May 22, 2023
Transcription
is
the
fundamental
process
of
gene
expression,
which
in
eukaryotes
occurs
within
complex
physicochemical
environment
nucleus.
Decades
research
have
provided
extreme
detail
molecular
and
functional
mechanisms
transcription,
but
spatial
genomic
organization
transcription
remains
mysterious.
Recent
discoveries
show
that
transcriptional
components
can
undergo
phase
separation
create
distinct
compartments
inside
nucleus,
providing
new
models
through
to
view
eukaryotes.
In
this
review,
we
focus
on
condensates
their
separation-like
behaviors.
We
suggest
differentiation
between
physical
descriptions
dynamic
biomolecular
assemblies
required
for
productive
discuss
how
are
central
organizing
three-dimensional
genome
across
temporal
scales.
Finally,
map
approaches
therapeutic
manipulation
ask
what
technical
advances
needed
understand
more
completely.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: May 15, 2024
Abstract
Stress
granules
(SGs)
are
induced
by
various
environmental
stressors,
resulting
in
their
compositional
and
functional
heterogeneity.
SGs
play
a
crucial
role
the
antiviral
process,
owing
to
potent
translational
repressive
effects
ability
trigger
signal
transduction;
however,
it
is
poorly
understood
how
these
differ
from
other
stressors.
Here
we
identify
that
TRIM25,
known
driver
of
ubiquitination-dependent
innate
immune
response,
critical
marker
SGs.
TRIM25
undergoes
liquid-liquid
phase
separation
(LLPS)
co-condenses
with
SG
core
protein
G3BP1
dsRNA-dependent
manner.
The
co-condensation
results
significant
enhancement
TRIM25’s
ubiquitination
activity
towards
multiple
proteins,
which
mainly
located
This
activating
RIG-I
signaling
pathway,
thus
restraining
RNA
virus
infection.
Our
studies
provide
conceptual
framework
for
better
understanding
heterogeneity
stress
granule
components
response
distinct
