Research Square (Research Square),
Год журнала:
2022,
Номер
unknown
Опубликована: Ноя. 21, 2022
Abstract
The
tetrameric
tumor
suppressor
p53
represents
a
great
challenge
for
3D-structural
analysis
due
to
its
high
degree
of
intrinsic
disorder
(ca.
40%).
We
aim
shed
light
on
the
structural
and
functional
roles
p53’s
C-terminal
region
in
full-length,
wild-type
human
tetramer
their
importance
DNA
binding.
For
this,
we
employed
complementary
techniques
mass
spectrometry
(MS)
an
integrated
approach
with
AI-based
computational
modeling.
Our
results
show
no
major
conformational
differences
between
DNA-bound
DNA-free
states,
but
reveal
substantial
compaction
region.
This
supports
proposed
mechanism
unspecific
binding
prior
transcription
initiation
by
specific
core
domain
p53.
synergies
MS
modeling
as
pursued
our
integrative
is
envisioned
serve
general
strategy
studying
intrinsically
disordered
proteins
(IDPs)
(IDRs).
Scientific Reports,
Год журнала:
2023,
Номер
13(1)
Опубликована: Май 25, 2023
Abstract
The
tetrameric
tumor
suppressor
p53
represents
a
great
challenge
for
3D-structural
analysis
due
to
its
high
degree
of
intrinsic
disorder
(ca.
40%).
We
aim
shed
light
on
the
structural
and
functional
roles
p53’s
C-terminal
region
in
full-length,
wild-type
human
tetramer
their
importance
DNA
binding.
For
this,
we
employed
complementary
techniques
mass
spectrometry
(MS)
an
integrated
approach
with
computational
modeling.
Our
results
show
no
major
conformational
differences
between
DNA-bound
DNA-free
states,
but
reveal
substantial
compaction
region.
This
supports
proposed
mechanism
unspecific
binding
prior
transcription
initiation
by
specific
core
domain
p53.
synergies
MS
modeling
as
pursued
our
integrative
is
envisioned
serve
general
strategy
studying
intrinsically
disordered
proteins
(IDPs)
(IDRs).
Journal of Molecular Cell Biology,
Год журнала:
2024,
Номер
16(1)
Опубликована: Янв. 1, 2024
Alternative
splicing
is
one
of
the
major
cellular
processes
that
determine
tissue-specific
expression
protein
variants.
However,
it
remains
challenging
to
identify
physiologically
relevant
and
tissue-selective
proteins
are
generated
by
alternative
splicing.
Hence,
we
investigated
target
spectrum
factor
Rbfox1
in
cardiac
muscle
context
more
detail.
By
using
a
combination
silico
prediction
in-cell
validation,
identified
several
focal
adhesion
as
targets
Rbfox1.
We
focused
on
patterns
vinculin
(metavinculin
isoform)
paxillin
(extended
both
potential
targets.
Minigene
analyses
suggested
isoforms
promoted
due
binding
introns.
Focal
adhesions
play
an
important
role
context,
since
they
mainly
influence
cell
shape,
cytoskeletal
organization,
cell-matrix
association.
Our
data
confirmed
depletion
changed
cardiomyoblast
morphology,
multinuclearity
after
differentiation,
which
might
be
changes
proteins.
our
results
indicate
promotes
genes
cells,
contribute
heart
disease
progression,
where
downregulation
frequently
observed.
The Journal of Physical Chemistry B,
Год журнала:
2024,
Номер
128(32), С. 7781 - 7791
Опубликована: Авг. 6, 2024
Much
attention
has
been
given
to
studying
the
translational
diffusion
of
globular
proteins,
whereas
intrinsically
disordered
proteins
(IDPs)
is
less
studied.
In
this
study,
we
investigate
and
how
it
affected
by
self-association
an
IDP,
κ-casein,
using
pulsed-field
gradient
nuclear
magnetic
resonance
time-resolved
Förster
energy
transfer.
Using
analysis
shape
attenuation
concentration
dependence
κ-casein
coefficients
intermolecular
interactions,
demonstrate
that
exhibits
continuous
self-association.
When
volume
fraction
below
0.08,
observe
results
in
a
macroscopic
phase
separation
upon
storage
at
4
°C.
At
fractions
above
leads
formation
labile
gel-like
networks
without
subsequent
separation.
Unlike
α-casein,
which
shows
strong
extensive
network
formation,
only
one-third
molecules
participate
gel
time,
resulting
more
dynamic
structure.
These
findings
highlight
unique
association
properties
contributing
better
understanding
its
behavior
under
various
conditions
potential
role
casein
micelle
formation.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Ноя. 11, 2022
Abstract
The
tetrameric
tumor
suppressor
p53
represents
a
great
challenge
for
3D-structural
analysis
due
to
its
high
degree
of
intrinsic
disorder
(ca.
40%).
We
aim
shed
light
on
the
structural
and
functional
roles
p53’s
C-terminal
region
in
full-length,
wild-type
human
tetramer
their
importance
DNA
binding.
For
this,
we
employed
complementary
techniques
mass
spectrometry
(MS)
an
integrated
approach
with
AI-based
computational
modeling.
Our
results
show
no
major
conformational
differences
between
DNA-bound
DNA-free
states,
but
reveal
substantial
compaction
region.
This
supports
proposed
mechanism
unspecific
binding
prior
transcription
initiation
by
specific
core
domain
p53.
synergies
MS
modeling
as
pursued
our
integrative
is
envisioned
serve
general
strategy
studying
intrinsically
disordered
proteins
(IDPs)
(IDRs).
