Nuclear speckle proteins form intrinsic and MALAT1-dependent microphases
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 27, 2025
Nuclear
speckles
are
enriched
in
serine
/
arginine
rich
splicing
factors
(SRSFs),
such
as
SRSF1.
Splicing
and
proteins
TDP-43
concentrate
into
distinct
speckle
territories
to
enable
pre-mRNA
processing.
We
have
discovered
that
SRSFs
block
copolymers
the
protein-specific
interplay
of
inter-block
repulsions
attractions
drives
spontaneous
microphase
separation.
This
gives
rise
size-limited,
ordered
assemblies,
30
-
45
nm
diameter.
Depending
on
protein,
each
comprises
several
tens
hundreds
molecules.
The
sub-micron
scale
observed
cells
shown
be
clusters
microphases.
regulatory
lncRNA
MALAT1
binds
preferentially
SRSF1
microphases
enhance
separation
alter
structures.
Microphase
enables
concentration
finite
numbers
assemblies
with
nanoscale
structures
can
modulated
by
.
Our
findings
provide
a
structural
framework
for
functional
organization
factors.
Language: Английский
Backbone-mediated weakening of pairwise interactions enables percolation in peptide-based mimics of protein condensates
Communications Chemistry,
Journal Year:
2025,
Volume and Issue:
8(1)
Published: April 6, 2025
Biomolecular
condensates
formed
by
intrinsically
disordered
proteins
(IDPs)
are
semidilute
solutions.
These
can
be
approximated
as
solutions
of
blob-sized
segments,
which
peptide-sized
motifs.
We
leveraged
the
blob
picture
and
molecular
dynamics
simulations
to
quantify
differences
between
inter-residue
interactions
in
model
compound
peptide-based
mimics
dense
versus
dilute
phases.
The
all-atom
use
a
polarizable
forcefield.
In
solutions,
aromatic
residues
stronger
than
cationic
residues.
This
holds
Cooperativity
within
phases
enhances
pairwise
leading
finite-sized
nanoscale
clusters.
results
for
paint
different
picture.
Backbone
amides
add
valence
associating
molecules.
While
this
phases,
it
weakens
pair
doing
so
concentration-dependent
manner.
Weakening
enables
fluidization
characterized
short-range
order
long-range
disorder.
higher
afforded
peptide
backbone
generates
system-spanning
networks.
As
result,
peptides
best
described
percolated
network
fluids.
Overall,
our
show
how
backbones
enhance
while
weakening
these
enable
percolation
Language: Английский