Conformational dynamics of the nuclear pore complex central channel
Yu Chen,
Guoli Zhou,
Miao Yu
и другие.
Biochemical Society Transactions,
Год журнала:
2025,
Номер
53(01)
Опубликована: Фев. 7, 2025
The
nuclear
pore
complex
(NPC)
is
a
vital
regulator
of
molecular
transport
between
the
nucleus
and
cytoplasm
in
eukaryotic
cells.
At
heart
NPC’s
function
are
intrinsically
disordered
phenylalanineglycine-rich
nucleoporins
(FG-Nups),
which
form
dynamic
permeability
barrier
within
central
channel.
This
nature
facilitates
efficient
nucleocytoplasmic
but
also
poses
significant
challenges
to
its
characterization,
especially
nano-confined
environment
NPC.
Recent
advances
experimental
techniques,
such
as
cryo-electron
microscopy,
atomic
force
fluorescence
magnetic
resonance,
along
with
computational
modeling,
have
illuminated
conformational
flexibility
FG-Nups,
underpins
their
functional
versatility.
review
synthesizes
these
advancements,
emphasizing
how
disruptions
FG-Nup
behavior—caused
by
mutations
or
pathological
interactions—contribute
diseases
neurodegenerative
disorders,
aging-related
decline,
viral
infections.
Despite
progress,
persist
deciphering
dynamics
crowded
cellular
environment,
under
conditions.
Addressing
gaps
critical
for
advancing
therapeutic
strategies
targeting
NPC
dysfunction
disease
progression.
Язык: Английский
Intrinsic stiffness and Θ-solvent regime in intrinsically disordered proteins: Implications for liquid-liquid phase separation
PNAS Nexus,
Год журнала:
2025,
Номер
4(2)
Опубликована: Фев. 1, 2025
Liquid-liquid
phase
separation
(LLPS)
exhibited
by
intrinsically
disordered
proteins
(IDPs)
depends
on
the
solvation
state
around
Θ-regime,
which
separates
good
from
poor
solvent.
Experimentally,
Θ-solvent
regime
of
finite
length
(N)
IDPs,
as
probed
small
angle
X-ray
scattering
(SAXS)
and
single
molecular
fluorescence
resonance
energy
transfer
(smFRET),
is
in
disagreement.
Using
computer
simulations
a
coarse-grained
IDP
model,
we
address
effect
chain
Θ-regime
IDPs
with
polar
side
chains
(polyglutamine)
hydrophobic
(polyleucine)
subject
to
varying
concentrations
cosolvents
[C]
,
urea
(denaturant)
or
trimethylamine
N-oxide
(protective
osmolyte)
water.
Due
their
intrinsic
stiffness,
these
are
always
expanded
short-length
scales,
independent
solvent
quality.
As
result,
for
short
sequences
(
≈10
25
residues),
propensity
exhibit
LLPS
cannot
be
inferred
single-chain
properties.
Further,
finite-size
cosolvent
concentration
attain
[CΘ]
)
extracted
structure
factor
emulating
SAXS
pair
distances
mimicking
smFRET
differs.
They
converge
same
only
at
large
N,
indicating
that
size
corrections
vary
different
We
show
radius
gyration
Rg
satisfies
scaling
relation
Rg2=Nf(cN)
can
exploited
accurately
extract
c=([C]/[CΘ]-1)
).
demonstrate
importance
aspects
originating
stiffness
thermal
blob
analyzing
properties
identify
regime.
Язык: Английский