Peptide-Mediated Liquid-Liquid Phase Separation and Biomolecular Condensates
Soft Matter,
Год журнала:
2025,
Номер
21(10), С. 1781 - 1812
Опубликована: Янв. 1, 2025
Peptide-mediated
liquid–liquid
phase
separation
(LLPS)
underpins
the
formation
of
dynamic
biomolecular
condensates,
regulated
by
diverse
molecular
interactions,
and
highlights
potential
applications
in
drug
delivery
synthetic
biology.
Язык: Английский
Charge Arrangement Determines the Sensitivity of Aggregation Patterns between Peptide-Chains to the Surrounding Ionic Environment
Journal of Chemical Information and Modeling,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 6, 2025
The
molecular
basis
for
the
liquid-liquid
phase
separation
(LLPS)
behavior
of
various
biomolecular
components
in
cell
is
formation
multivalent
and
low-affinity
interactions.
When
content
these
exceeds
a
certain
critical
concentration,
molecules
will
spontaneously
coalesce
to
form
new
liquid
phase;
i.e.,
LLPS
occurs.
Intrinsically
disordered
proteins
(IDPs)
are
usually
rich
amino
acids
with
charged
side-chains,
thus,
LLPS-involving
interactions
between
their
side-chains
great
interest.
However,
details
coalescence
such
IDPs
salt
solution
still
lacking.
Here,
we
focus
on
two
types
peptide-chains
oppositely
extreme
arrangements
investigate
aggregation
patterns
ionic
environments.
results
show
that
interaction
nonuniform
charge
arrangement
sequences
more
sensitive
surrounding
cationic
environment,
Na+
ions
likely
cause
ASP
residues
compared
Mg2+
ions.
As
concentration
increases,
electrostatic
gradually
converted
into
negative-negative
acid
network
bridged
by
ions,
while
positive
charge-rich
regions
strongly
inclined
be
exposed
solvent
environment
gain
greater
freedom
movement.
Simultaneously,
this
effect
reach
saturation
further
increase
concentration.
present
study
enriches
insights
dominant
factors
phenomena
at
atomic
level,
which
hopefully
inspire
design
application
targeted
future.
Язык: Английский
Accelerated amyloid fibril formation at the interface of liquid–liquid phase‐separated droplets by depletion interactions
Protein Science,
Год журнала:
2025,
Номер
34(2)
Опубликована: Янв. 28, 2025
Abstract
Amyloid
fibril
formation
of
α‐synuclein
(αSN)
is
a
hallmark
synucleinopathies.
Although
the
previous
studies
have
provided
numerous
insights
into
molecular
basis
αSN
amyloid
formation,
it
remains
unclear
how
self‐assembles
fibrils
in
vivo.
Here,
we
show
that
accelerated
presence
two
macromolecular
crowders,
polyethylene
glycol
(PEG)
(MW:
~10,000)
and
dextran
(DEX)
~500,000),
with
maximum
at
approximately
7%
(w/v)
PEG
DEX.
Under
these
conditions,
crowders
induce
two‐phase
separation
upper
lower
DEX
phases
small
number
liquid
droplets
phases,
respectively.
Fluorescence
microscope
images
revealed
interfaces
phase
are
major
sites
formation.
We
consider
depletion
interactions
working
micro
phase‐segregated
state
systems
causes
condensation
interface
between
solute
droplets,
resulting
Ultrasonication
further
both
confirming
droplet‐dependent
Similar
PEG/DEX‐dependent
was
observed
for
β
peptide.
In
contrast,
2
‐microglobulin
or
hen
egg
white
lysozyme
native
fold
suppressed
PEG/DEX
mixtures,
suggesting
work
adversely
depending
on
whether
protein
unfolded
folded.
Язык: Английский
Mechanism of amyloid fibril formation triggered by breakdown of supersaturation
Deleted Journal,
Год журнала:
2025,
Номер
2(1)
Опубликована: Фев. 3, 2025
Язык: Английский
ATP‐Regulated Formation of Transient Peptide Amphiphiles Superstructures
Small,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Abstract
Self‐assembly
of
biotic
systems
serves
as
inspiration
for
the
preparation
synthetic
supramolecular
assemblies
to
mimic
structural,
temporal,
and
functional
aspects
living
systems.
Despite
peptide
amphiphiles
(PAs)
being
widely
studied
in
context
biomimetic
bioactive
nanomaterials,
very
little
is
currently
known
about
reversible
spatiotemporal
control
their
hierarchical
self‐assemblies.
Here,
it
shown
that
PA‐based
nanofibers
can
transiently
form
superstructures,
through
binding
with
oppositely
charged
adenosine
triphosphate
(ATP),
leading
charge
screening
stabilization
bundled
nanofibers.
Enzymatic
hydrolysis
ATP
monophosphate
phosphates
causes
disassembly
superstructures
recovery
individual
The
lifetime
be
controlled
by
adjusting
concentration
either
or
enzyme.
role
formation
PA
has
on
chemical
reactivity
catalysis
also
evaluated.
It
observed
superstructuration
responsible
downregulation
activity,
which
then
recovered
gradual
bundles.
These
results
demonstrate
potential
self‐assembly
modulate
nanostructures.
Язык: Английский
Clues to the Design of Aggregation-Resistant Insulin from Proline Scanning of Highly Amyloidogenic Peptides Derived from the N-Terminal Segment of the A-Chain
Molecular Pharmaceutics,
Год журнала:
2024,
Номер
21(4), С. 2025 - 2033
Опубликована: Март 25, 2024
Insulin
aggregation
poses
a
significant
problem
in
pharmacology
and
medicine
as
it
occurs
during
prolonged
storage
of
the
hormone
vivo
at
insulin
injection
sites.
We
have
recently
shown
that
dominant
forces
driving
self-assembly
fibrils
are
likely
to
arise
from
intermolecular
interactions
involving
N-terminal
segment
A-chain
(ACC1–13).
Here,
we
study
how
proline
substitutions
within
pilot
GIVEQ
sequence
this
fragment
affect
its
propensity
aggregate
both
neutral
acidic
environments.
In
reasonable
agreement
with
silico
prediction
based
on
Cordax
algorithm,
positions
3,
4,
5
turn
out
be
very
effective
preventing
according
thioflavin
T-fluorescence-based
kinetic
assay,
infrared
spectroscopy,
atomic
force
microscopy
(AFM).
Since
valine
glutamate
side
chains
strongly
involved
receptor,
focused
possible
implications
Q
→
P
substitution
for
insulin's
stability
receptor.
To
end,
comparative
molecular
dynamics
(MD)
simulations
Q5P
mutant
wild-type
were
carried
free
receptor-bound
(site
1)
monomers.
The
results
point
mild
destabilization
vis
à
monomer,
well
partial
preservation
key
contacts
complex
between
discuss
these
findings
context
design
aggregation-resistant
analogues
retaining
hormonal
activity.
Язык: Английский
Unraveling the Hydration Dynamics of the ACC1-13K24-ATP System: From Liquid-to-Droplet to-Amyloid Fibril
Biophysical Journal,
Год журнала:
2024,
Номер
123(22), С. 3863 - 3870
Опубликована: Сен. 11, 2024
Язык: Английский
Understanding and fine tuning the propensity of ATP-driven liquid–liquid phase separation with oligolysine
Physical Chemistry Chemical Physics,
Год журнала:
2024,
Номер
26(14), С. 10568 - 10578
Опубликована: Янв. 1, 2024
Liquid–liquid
phase
separation
(LLPS)
plays
a
pivotal
role
in
the
organization
and
functionality
of
living
cells.
Язык: Английский
Mechanistic Insights into the c-MYC G-Quadruplex and Berberine Binding inside an Aqueous Two-Phase System Mimicking Biomolecular Condensates
The Journal of Physical Chemistry Letters,
Год журнала:
2024,
Номер
15(34), С. 8706 - 8714
Опубликована: Авг. 19, 2024
We
investigated
the
binding
between
c-MYC
G-quadruplex
(GQ)
and
berberine
chloride
(BCl)
in
an
aqueous
two-phase
system
(ATPS)
with
12.3
wt
%
polyethylene
glycol
5.6
dextran,
mimicking
highly
crowded
intracellular
biomolecular
condensates
formed
via
liquid–liquid
phase
separation.
found
that
ATPS,
complex
formation
is
significantly
altered,
leading
to
increase
affinity
a
change
stoichiometry
of
respect
neat
buffer
conditions.
Thermodynamic
studies
reveal
becomes
more
thermodynamically
favorable
ATPS
due
entropic
effects,
as
strong
excluded
volume
effect
inside
droplets
reduces
penalty
associated
binding.
Finally,
BCl
for
GQ
higher
than
those
other
DNA
structures,
indicating
potential
specific
interactions.
Overall,
these
findings
will
be
helpful
design
drugs
targeting
structures
cancer-related
biocondensates.
Язык: Английский