bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 27, 2023
Poly(ADP-ribose)
(PAR),
as
part
of
a
post-translational
modification,
serves
flexible
scaffold
for
noncovalent
protein
binding.
Such
binding
is
influenced
by
PAR
chain
length
through
mechanism
yet
to
be
elucidated.
Structural
insights
have
been
elusive,
partly
due
the
difficulties
associated
with
synthesizing
chains
defined
lengths.
Here,
we
employ
an
integrated
approach
combining
molecular
dynamics
(MD)
simulations
small-angle
X-ray
scattering
(SAXS)
experiments,
enabling
us
identify
highly
heterogeneous
ensembles
conformers
at
two
different,
physiologically
relevant
lengths:
Computational and Structural Biotechnology Journal,
Journal Year:
2024,
Volume and Issue:
23, P. 3143 - 3154
Published: Aug. 2, 2024
The
zinc-finger
antiviral
protein
(ZAP)
is
an
innate
immunity
sensor
of
non-self
nucleic
acids.
Its
activity
exerted
through
the
physical
interaction
with
different
cofactors,
including
TRIM25,
Riplet
and
KHNYN.
Cellular
proteins
that
interact
infectious
agents
are
expected
to
be
engaged
in
genetic
conflicts
often
result
their
rapid
evolution.
To
test
this
possibility
identify
regions
most
strongly
targeted
by
natural
selection,
we
applied
silico
molecular
evolution
tools
analyze
evolutionary
history
ZAP
cofactors
four
mammalian
groups.
We
report
evidence
positive
selection
all
genes
On
average,
intrinsically
disordered
(IDRs)
embedded
evolve
significantly
faster
than
folded
domains
positively
selected
sites
fall
within
IDRs.
In
ZAP,
PARP
domain
also
shows
abundant
signals
independent
groups
suggests
modulation
its
ADP-ribose
binding
ability.
Detailed
analyses
biophysical
properties
IDRs
revealed
chain
compaction
conformational
entropy
conserved
across
mammals.
KHNYN
particularly
compact,
indicating
they
may
promote
phase
separation
(PS).
line
hypothesis,
predicted
several
PS-promoting
KHNYN,
as
well
TRIM25.
Positively
these
regions,
suggesting
PS
important
for
functions
arms
race
viruses.
Our
data
shed
light
into
indicate
represent
central
elements
host-pathogen
interactions.
Biosensors,
Journal Year:
2023,
Volume and Issue:
13(7), P. 723 - 723
Published: July 10, 2023
This
work
reports
the
development
of
a
fluorescence
method
for
detection
poly(ADP-ribose)
polymerase-1
(PARP1),
in
which
phenylboronic
acid-modified
fluorescein
isothiocyanate
dye
(FITC-PBA)
was
used
to
recognize
formed
(PAR)
polymer.
The
system
designed
by
conjugating
recombinant
streptavidin
(rSA)
with
PARP1-specific
double-stranded
DNA
(dsDNA)
through
streptavidin-biotin
interaction.
Capture
PARP1
via
rSA-biotin-dsDNA
allowed
poly-ADP-ribosylation
(PARylation)
both
rSA
and
homogeneous
solution.
resulting
rSA-biotin-dsDNA/PAR
conjugates
were
then
captured
separated
commercialized
nitrilotriacetic
acid-nickel
ion-modified
magnetic
bead
(MB-NTA-Ni)
interaction
between
NTA-Ni
on
MB
surface
oligohistidine
(His6)
tag
rSA.
PAR
polymer
could
capture
FITC-PBA
borate
ester
boronic
acid
moiety
PBA
cis-diol
group
ribose,
thus
causing
decrease
signal.
PARylation
influence
steric
hindrance
efficiency
confirmed
using
reasonable
strategies.
showed
wide
linear
range
(0.01~20
U)
low
limit
(0.01
U).
should
be
valuable
novel
biosensors
polymerases
diol-containing
species.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(12), P. 2808 - 2808
Published: Dec. 11, 2024
The
nervous
system
is
susceptible
to
DNA
damage
and
repair
defects,
if
not
repaired,
neuronal
cells
can
die,
causing
neurodegenerative
diseases
in
humans.
overall
picture
of
what
known
about
mechanisms
the
still
unclear.
current
challenge
use
accumulated
knowledge
basic
science
on
improve
treatment
disorders.
In
this
review,
we
summarize
understanding
function
repair,
particular,
base
excision
double-strand
break
pathways
as
being
most
important
cells.
We
recent
data
proteins
involved
associated
with
diseases,
particular
emphasis
PARP1
ND-associated
proteins,
which
are
have
ability
undergo
liquid–liquid
phase
separation.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 27, 2023
Poly(ADP-ribose)
(PAR),
as
part
of
a
post-translational
modification,
serves
flexible
scaffold
for
noncovalent
protein
binding.
Such
binding
is
influenced
by
PAR
chain
length
through
mechanism
yet
to
be
elucidated.
Structural
insights
have
been
elusive,
partly
due
the
difficulties
associated
with
synthesizing
chains
defined
lengths.
Here,
we
employ
an
integrated
approach
combining
molecular
dynamics
(MD)
simulations
small-angle
X-ray
scattering
(SAXS)
experiments,
enabling
us
identify
highly
heterogeneous
ensembles
conformers
at
two
different,
physiologically
relevant
lengths:
