bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 11, 2024
We
develop
a
surrogate
model
for
low
complexity
disordered
proteins,
which
allows
us
to
generate
sequences
with
quantifiable
disorder.
investigate
properties
of
these
sequences,
and
show
that
the
sequence
dependence
radius
gyration
only
arises
in
vicinity
polymer
collapse
transition.
Microphase
propensity
is
shown
be
reliable
predictor,
outperforming
state
art
methods,
crossover
region.
predictions
associative
theory
as
limiting
case,
discuss
its
applicability.
Journal of Cell Science,
Год журнала:
2023,
Номер
136(24)
Опубликована: Дек. 15, 2023
Liquid-liquid
phase
separation
is
a
major
mechanism
for
organizing
macromolecules,
particularly
proteins
with
intrinsically
disordered
regions,
in
compartments
not
limited
by
membrane
or
scaffold.
The
cell
can
therefore
be
perceived
as
complex
emulsion
containing
many
of
these
membraneless
organelles,
also
referred
to
biomolecular
condensates,
together
numerous
membrane-bound
organelles.
It
currently
unclear
how
such
concoction
operates
allow
intracellular
trafficking,
signaling
and
metabolic
processes
occur
high
spatiotemporal
precision.
Based
on
experimental
observations
synaptic
vesicle
condensates
-
organelle
that
fact
packed
membranes
we
present
here
the
framework
dipping
contacts:
novel
type
contact
site
between
organelles
membranes.
In
this
Hypothesis,
propose
our
contacts
serve
foundation
investigate
interface
couples
diffusion
material
properties
biochemical
occurring
identity
regulation
especially
critical
case
neurodegenerative
diseases,
where
aberrant
inclusions
misfolded
damaged
underlie
cellular
pathology.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 19, 2023
Abstract
Although
our
understanding
of
the
involvement
heterochromatin
architectural
factors
in
shaping
nuclear
organization
is
improving,
there
still
ongoing
debate
regarding
role
active
genes
this
process.
In
study,
we
utilize
publicly-available
Micro-C
data
from
mouse
embryonic
stem
cells
to
investigate
relationship
between
gene
transcription
and
3D
folding.
Our
analysis
uncovers
a
nonmonotonic
-
globally
positive
correlation
intragenic
contact
density
Pol
II
occupancy,
independent
cohesin-based
loop
extrusion.
Through
development
biophysical
model
integrating
dynamics
within
polymer
chromosome
organization,
demonstrate
that
II-mediated
attractive
interactions
with
limited
valency
transcribed
regions
yield
quantitative
predictions
consistent
chromosome-conformation-capture
live-imaging
experiments.
work
provides
compelling
evidence
transcriptional
activity
shapes
4D
genome
through
micro-compartmentalization.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Авг. 23, 2023
Abstract
Intrinsically
disordered
proteins
(IDPs)
frequently
mediate
liquid-liquid
phase
separation
(LLPS)
that
underlies
the
formation
of
membraneless
organelles.
Together
with
theory
and
experiment,
efficient
coarse-grained
(CG)
simulations
have
been
instrumental
in
understanding
sequence-
specific
IDPs.
However,
widely-used
Cα-only
models
are
severely
limited
capturing
peptide
nature
IDPs,
including
backbone-mediated
interactions
effects
secondary
structures,
LLPS.
Here,
we
describe
a
hybrid
resolution
(HyRes)
protein
model
for
accurate
description
backbone
transient
structures
With
an
atomistic
side
chains,
HyRes
accurately
predicts
residue
helical
propensity
chain
dimension
monomeric
Using
GY-23
as
system,
show
is
enough
direct
simulation
spontaneous
separation,
at
same
time
to
resolve
single
mutations.
also
successfully
predict
increased
beta-sheet
condensate,
consistent
available
experimental
data.
We
further
utilize
study
TPD-43,
where
several
disease-related
mutants
conserved
region
(CR)
shown
affect
residual
helicities
modulate
LLPS
propensity.
The
recapitulate
effect
these
on
helicity
TDP-43
CR.
Analyses
reveal
balance
between
sidechain-mediated
interactions,
but
not
itself,
actually
determines
believe
represents
important
advance
molecular
will
help
elucidate
coupling
IDP
separation.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 11, 2024
We
develop
a
surrogate
model
for
low
complexity
disordered
proteins,
which
allows
us
to
generate
sequences
with
quantifiable
disorder.
investigate
properties
of
these
sequences,
and
show
that
the
sequence
dependence
radius
gyration
only
arises
in
vicinity
polymer
collapse
transition.
Microphase
propensity
is
shown
be
reliable
predictor,
outperforming
state
art
methods,
crossover
region.
predictions
associative
theory
as
limiting
case,
discuss
its
applicability.
