Scientific Reports,
Год журнала:
2023,
Номер
13(1)
Опубликована: Авг. 16, 2023
Single
molecule
localization
microscopy
offers
resolution
nearly
down
to
the
molecular
level
with
specific
labelling,
and
is
thereby
a
promising
tool
for
structural
biology.
In
practice,
however,
actual
value
this
field
limited
primarily
by
incomplete
fluorescent
labelling
of
structure.
This
missing
information
can
be
completed
merging
from
many
structurally
identical
particles
in
particle
fusion
approach
similar
cryo-EM
single-particle
analysis.
paper,
we
present
data
analysis
results
fluorescently
labelled
Nup96
nucleoporins
Nuclear
Pore
Complex
show
that
occurs
spatial
arrangement
two
rings
8
units
copies
per
unit
giving
total
32
pore.
We
use
Artificial
Intelligence
assisted
modeling
Alphafold
extend
existing
model
accurately
pinpoint
positions
labels
accuracy
match
between
better
than
3
nm
in-plane
5
out-of-plane.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Ноя. 10, 2023
Abstract
Proper
subcellular
localization
is
crucial
for
the
functioning
of
biomacromolecules,
including
proteins
and
RNAs.
Nuclear
transport
a
fundamental
cellular
process
that
regulates
many
macromolecules
within
nuclear
or
cytoplasmic
compartments.
In
humans,
approximately
60
are
involved
in
transport,
nucleoporins
form
membrane-embedded
pore
complexes,
karyopherins
cargoes
through
these
Ran
system
ensure
directed
rapid
transport.
Many
play
additional
essential
roles
mitosis,
biomolecular
condensation,
gene
transcription.
Dysregulation
linked
to
major
human
diseases
such
as
cancer,
neurodegenerative
diseases,
viral
infections.
Selinexor
(KPT-330),
an
inhibitor
targeting
export
factor
XPO1
(also
known
CRM1),
was
approved
2019
treat
two
types
blood
cancers,
dozens
clinical
trials
ongoing.
This
review
summarizes
three
decades
research
data
this
field
but
focuses
on
structure
function
individual
from
recent
studies,
providing
cutting-edge
holistic
view
role
health
disease.
In-depth
knowledge
rapidly
evolving
has
potential
bring
new
insights
into
biology,
pathogenic
mechanisms,
therapeutic
approaches.
Viruses,
Год журнала:
2025,
Номер
17(2), С. 151 - 151
Опубликована: Янв. 23, 2025
Viruses
frequently
exploit
the
host’s
nucleocytoplasmic
trafficking
machinery
to
facilitate
their
replication
and
evade
immune
defenses.
By
encoding
specialized
proteins
other
components,
they
strategically
target
host
nuclear
transport
receptors
(NTRs)
nucleoporins
within
spiderweb-like
inner
channel
of
pore
complex
(NPC),
enabling
efficient
access
nucleus.
This
review
explores
intricate
mechanisms
governing
import
export
viral
with
a
focus
on
interplay
between
factors
determinants
that
are
essential
for
these
processes.
Given
pivotal
role
shuttling
in
life
cycle,
we
also
examine
therapeutic
strategies
aimed
at
disrupting
pathways.
includes
evaluating
efficacy
pharmacological
inhibitors
impairing
assessing
potential
as
antiviral
treatments.
Furthermore,
emphasize
need
continued
research
develop
targeted
therapies
leverage
vulnerabilities
trafficking.
Emerging
high-resolution
techniques,
such
advanced
imaging
computational
modeling,
transforming
our
understanding
dynamic
interactions
viruses
NPC.
These
cutting-edge
tools
driving
progress
identifying
novel
opportunities
uncovering
deeper
insights
into
pathogenesis.
highlights
importance
advancements
paving
way
innovative
strategies.
Biochemical Society Transactions,
Год журнала:
2023,
Номер
51(2), С. 871 - 886
Опубликована: Апрель 26, 2023
Nuclear
pore
complexes
(NPCs)
mediate
the
exchange
of
materials
between
nucleoplasm
and
cytoplasm,
playing
a
key
role
in
separation
nucleic
acids
proteins
into
their
required
compartments.
The
static
structure
NPC
is
relatively
well
defined
by
recent
cryo
EM
other
studies.
functional
roles
dynamic
components
NPC,
phenylalanyl-glycyl
(FG)
repeat
rich
nucleoporins,
less
clear
because
our
limited
understanding
highly
protein
systems.
These
form
restrained
concentrate
which
interacts
with
concentrates
nuclear
transport
factors
(NTRs)
to
provide
facilitated
nucleocytoplasmic
cargoes.
Very
rapid
among
FG
repeats
NTRs
supports
extremely
fast
transport,
close
rate
macromolecular
diffusion
while
without
specific
interactions
are
entropically
excluded,
though
details
on
several
aspects
mechanism
behaviors
remain
be
resolved.
However,
as
discussed
here,
new
technical
approaches
combined
more
advanced
modeling
methods
will
likely
an
improved
description
potentially
at
atomic
level
near
future.
Such
advances
major
benefit
comprehending
malfunctioning
plays
cancer,
aging,
viral
diseases,
neurodegeneration.
Cells,
Год журнала:
2024,
Номер
13(3), С. 279 - 279
Опубликована: Фев. 2, 2024
Nuclear
pore
complexes
(NPCs)
on
the
nuclear
membrane
surface
have
a
crucial
function
in
controlling
movement
of
small
molecules
and
macromolecules
between
cell
nucleus
cytoplasm
through
their
intricate
core
channel
resembling
spiderweb
with
several
layers.
Currently,
there
are
few
methods
available
to
accurately
measure
dynamics
pores
membranes
at
nanoscale.
The
limitation
traditional
optical
imaging
is
due
diffraction,
which
prevents
achieving
required
resolution
for
observing
diverse
array
organelles
proteins
within
cells.
Super-resolution
techniques
effectively
addressed
this
constraint
by
enabling
observation
subcellular
components
Nevertheless,
it
acknowledge
that
these
often
need
use
fixed
samples.
This
also
raises
question
how
closely
static
image
represents
real
intracellular
dynamic
system.
High-speed
atomic
force
microscopy
(HS-AFM)
unique
technique
used
field
structural
biology,
study
individual
motion
close
native
states.
Establishing
reliable
repeatable
mammalian
tissue
nanoscale
using
HS-AFM
remains
challenging
inadequate
sample
preparation.
presents
rapid
strainer
microfiltration
(RSM)
protocol
directly
preparing
high-quality
nuclei
from
mouse
brain.
Subsequently,
we
promptly
utilize
real-time
cinematography
approaches
record
spatiotemporal
nano-dynamics
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 4, 2024
SUMMARY
ALS
and
FTD
are
complex
neurodegenerative
disorders
that
primarily
affects
motor
neurons
in
the
brain
spinal
cord,
cortical
frontal
lobe.
Although
pathogenesis
of
ALS/FTD
is
unclear,
recent
research
spotlights
nucleocytoplasmic
transport
impairment,
DNA
damage,
nuclear
abnormalities
as
drivers
neuronal
death.
In
this
study,
we
show
loss
envelope
(NE)
integrity
a
key
pathology
associated
with
pore
(NPC)
injury
C9ORF72
mutant
neurons.
Importantly,
mechanical
stresses
generated
by
cytoskeletal
forces
on
NE
can
lead
to
NPC
injury,
integrity,
accumulation
damage.
demonstrate
restoring
tensional
homeostasis,
disconnecting
nucleus
from
cytoskeleton,
rescue
reduce
damage
cells.
Together,
our
data
suggest
modulation
homeostasis
repair
may
represent
novel
promising
therapeutic
target
for
ALS/FTD.
FEBS Letters,
Год журнала:
2023,
Номер
597(20), С. 2519 - 2533
Опубликована: Окт. 1, 2023
Ran‐binding
protein
2
(RANBP2)/Nup358
is
a
nucleoporin
and
key
component
of
the
nuclear
pore
complex.
Through
its
multiple
functions
(e.g.,
SUMOylation,
regulation
nucleocytoplasmic
transport)
subcellular
localizations
at
envelope,
kinetochores,
annulate
lamellae),
it
involved
in
many
cellular
processes.
RANBP2
dysregulation
or
mutation
leads
to
development
human
pathologies,
such
as
acute
necrotizing
encephalopathy
1,
cancer,
neurodegenerative
diseases,
also
viral
infections.
The
chromosomal
region
containing
gene
highly
dynamic,
with
high
structural
variation
recombination
events
that
led
appearance
family
called
GCC2
Protein
Domains
(
RGPD
),
loss/duplication
during
ape
evolution.
Although
homoplasy
maintenance
evolution
suggest
they
might
confer
an
advantage
their
hosts,
are
still
unknown
understudied.
In
this
review,
we
discuss
importance
metazoans
function‐related
caused
by
alteration
expression
levels
(through
promotor
activity,
post‐transcriptional,
post‐translational
modifications),
localization,
genetic
mutations.
