Annual Review of Virology,
Год журнала:
2023,
Номер
10(1), С. 163 - 182
Опубликована: Апрель 11, 2023
Phase
separation
of
viral
biopolymers
is
a
key
factor
in
the
formation
cytoplasmic
inclusions,
known
as
sites
virus
replication
and
assembly.
This
review
describes
mechanisms
factors
that
affect
phase
identifies
potential
areas
for
future
research.
Drawing
inspiration
from
studies
on
cellular
RNA-rich
condensates,
we
compare
hierarchical
coassembly
ribosomal
RNAs
proteins
nucleolus
to
coordinated
taking
place
within
factories
viruses
containing
segmented
RNA
genomes.
We
highlight
common
characteristics
biomolecular
condensates
how
this
new
understanding
reshaping
our
views
assembly
mechanisms.
Such
have
uncover
unexplored
antiviral
strategies
targeting
these
phase-separated
states.
PLoS Computational Biology,
Год журнала:
2023,
Номер
19(5), С. e1010652 - e1010652
Опубликована: Май 15, 2023
Liquid
condensate
droplets
with
distinct
compositions
of
proteins
and
nucleic
acids
are
widespread
in
biological
cells.
While
it
is
known
that
such
droplets,
or
compartments,
can
regulate
irreversible
protein
aggregation,
their
effect
on
reversible
self-assembly
remains
largely
unexplored.
In
this
article,
we
use
kinetic
theory
solution
thermodynamics
to
investigate
the
liquid-liquid
phase
separation
structures
well-defined
sizes
architectures.
We
find
that,
when
assembling
subunits
preferentially
partition
into
liquid
robustness
against
traps
maximum
achievable
assembly
rates
be
significantly
increased.
particular,
both
range
conditions
leading
productive
corresponding
increase
by
orders
magnitude.
analyze
rate
equation
predictions
using
simple
scaling
estimates
identify
effects
as
a
function
relevant
control
parameters.
These
results
may
elucidate
processes
underlie
normal
cellular
functions
pathogenesis,
suggest
strategies
for
designing
efficient
bottom-up
nanomaterials
applications.
Journal of Cellular Biochemistry,
Год журнала:
2024,
Номер
125(3)
Опубликована: Фев. 13, 2024
Abstract
When
the
SARS‐CoV‐2
virus
infects
humans,
it
leads
to
a
condition
called
COVID‐19
that
has
wide
spectrum
of
clinical
manifestations,
from
no
symptoms
acute
respiratory
distress
syndrome.
The
initiates
damage
by
attaching
ACE‐2
protein
on
surface
endothelial
cells
line
blood
vessels
and
using
these
as
hosts
for
replication.
Reactive
oxygen
species
levels
are
increased
during
viral
replication,
which
oxidative
stress.
About
three‐fifths
(~60%)
people
who
get
infected
with
eradicate
their
body
after
28
days
recover
normal
activity.
However,
large
fraction
(~40%)
suffer
various
(anosmia
and/or
ageusia,
fatigue,
cough,
myalgia,
cognitive
impairment,
insomnia,
dyspnea,
tachycardia)
beyond
12
weeks
diagnosed
syndrome
long
COVID.
Long‐term
studies
in
group
contracted
have
been
contrasted
noninfected
matched
people.
A
subset
can
be
distinguished
set
cytokine
markers
persistent,
low‐grade
inflammation
often
self‐report
two
or
more
bothersome
symptoms.
No
medication
alleviate
efficiently.
Coronavirus
nucleocapsid
proteins
investigated
extensively
potential
drug
targets
due
key
roles
among
is
ability
bind
respective
genomic
RNAs
incorporation
into
emerging
virions.
This
review
highlights
basic
its
undergo
liquid–liquid
phase
separation.
We
hypothesize
this
separation
may
contribute
hypothesis
unlocks
new
investigation
angles
could
potentially
open
novel
avenues
better
understanding
COVID
treating
condition.
Cell Reports,
Год журнала:
2022,
Номер
40(8), С. 111251 - 111251
Опубликована: Авг. 1, 2022
Membraneless
biomolecular
condensates
(BMCs)
contribute
to
the
replication
of
a
growing
number
viruses
but
remain
be
functionally
characterized.
Previously,
we
demonstrated
that
pan-retroviral
nucleocapsid
(NC)
proteins
phase
separated
into
regulating
virus
assembly.
Here
discover
intrinsically
disordered
human
immunodeficiency
virus-type
1
(HIV-1)
core
condense
with
viral
genomic
RNA
(vRNA)
assemble
as
BMCs
attaining
geometry
characteristic
reverse
transcription
complexes.
We
explore
predisposition,
mechanisms,
and
pharmacologic
sensitivity
HIV-1
in
living
cells.
vRNA-interacting
NC
were
found
scaffolds
onto
which
client
capsid,
transcriptase,
integrase
assemble.
exhibit
fundamental
characteristics
are
drug-sensitive.
Lastly,
protease-mediated
maturation
Gag
Gag-Pol
precursor
yield
abundant
visible
This
study
redefines
components
fluid
advances
our
understanding
nature
cores
during
ingress.
Current Research in Structural Biology,
Год журнала:
2022,
Номер
4, С. 285 - 307
Опубликована: Янв. 1, 2022
Protein
conformation
and
cell
compartmentalization
are
fundamental
concepts
subjects
of
vast
scientific
endeavors.
In
the
last
two
decades,
we
have
witnessed
exciting
advances
that
unveiled
conjunction
these
concepts.
An
avalanche
studies
highlighted
central
role
biomolecular
condensates
in
membraneless
subcellular
permits
spatiotemporal
organization
regulation
myriads
simultaneous
biochemical
reactions
macromolecular
interactions.
These
also
shown
condensation,
driven
by
multivalent
intermolecular
interactions,
is
mediated
order-disorder
transitions
protein
domain
architecture.
Conceptually,
condensation
a
distinct
level
conformational
landscape
which
collective
folding
large
collections
molecules
takes
place.
Biomolecular
arise
physical
process
phase
separation
comprise
variety
bodies
ranging
from
organelles
to
liquid
solid-like
conglomerates,
spanning
lengths
mesoscopic
clusters
(nanometers)
micrometer-sized
objects.
this
review,
summarize
discuss
recent
work
on
assembly,
composition,
conformation,
material
properties,
thermodynamics,
regulation,
functions
bodies.
We
review
conceptual
framework
for
future
dynamics
condensed
proteins
cellular
processes.
Journal of Virology,
Год журнала:
2023,
Номер
97(2)
Опубликована: Фев. 7, 2023
Viruses
often
condense
the
materials
needed
for
their
replication
into
discrete
intracellular
factories.
For
rotaviruses,
agents
of
severe
gastroenteritis
in
children,
factory
formation
is
mediated
part
by
an
octameric
protein
called
NSP2.
Nature Biotechnology,
Год журнала:
2022,
Номер
41(4), С. 552 - 559
Опубликована: Окт. 10, 2022
Abstract
The
formation
of
macromolecular
complexes
can
be
measured
by
detection
changes
in
rotational
mobility
using
time-resolved
fluorescence
anisotropy.
However,
this
method
is
limited
to
relatively
small
molecules
(~0.1–30
kDa),
excluding
the
majority
human
proteome
and
its
complexes.
We
describe
selective
anisotropy
with
reversibly
switchable
states
(STARSS),
which
overcomes
limitation
extends
observable
mass
range
more
than
three
orders
magnitude.
STARSS
based
on
long-lived
reversible
molecular
transitions
fluorescent
proteins
resolve
slow
diffusivity
large
used
probe
several
cells,
including
chromatin,
retroviral
Gag
lattice
activity-regulated
cytoskeleton-associated
protein
oligomers.
Because
arbitrarily
structures,
it
generally
applicable
entire
proteome.
PLoS Pathogens,
Год журнала:
2024,
Номер
20(3), С. e1012085 - e1012085
Опубликована: Март 14, 2024
Elaborate
viral
replication
organelles
(VROs)
are
formed
to
support
positive-strand
RNA
virus
in
infected
cells.
VRO
formation
requires
subversion
of
intracellular
membranes
by
proteins.
Here,
we
showed
that
the
key
ATG8f
autophagy
protein
and
NBR1
selective
receptor
were
co-opted
Tomato
bushy
stunt
(TBSV)
closely-related
carnation
Italian
ringspot
virus.
Knockdown
or
plants
led
reduced
tombusvirus
replication,
suggesting
pro-viral
function
for
autophagy.
BiFC
proximity-labeling
experiments
TBSV
p33
interacted
with
recruit
them
VROs.
In
addition,
observed
several
core
proteins,
such
as
ATG1a,
ATG4,
ATG5,
ATG101
plant-specific
SH3P2
adaptor
proteins
also
re-localized
VROs,
hijacks
machinery
plant
We
demonstrated
components
facilitated
recruitment
VPS34
PI3
kinase
enrichment
phospholipids,
phosphatidylethanolamine
PI3P
phosphoinositide
membranes.
Hijacking
into
VROs
inhibition
autophagic
flux.
found
a
fraction
subverted
was
sequestered
biomolecular
condensates
associated
propose
VRO-associated
trap
those
taking
away
from
pathway.
Overall,
tombusviruses
hijack
provide
phospholipid-rich
regulate
antiviral
