bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 15, 2024
Abstract
Tissue
maintenance
is
underpinned
by
resident
stem
cells
whose
activity
modulated
microenvironmental
cues.
Using
Drosophila
as
a
simple
model
to
identify
regulators
of
cell
behaviour
and
survival
in
vivo
,
we
have
identified
novel
connections
between
the
conserved
transmembrane
proteoglycan
Syndecan,
nuclear
properties
function.
In
midgut,
Syndecan
depletion
intestinal
results
their
loss
from
tissue,
impairing
tissue
renewal.
At
cellular
level,
alters
shape,
causes
lamina
invaginations
DNA
damage.
second
developing
brain,
live
imaging
revealed
that
neural
envelope
remodelling
defects
which
arise
upon
division.
Our
findings
reveal
new
role
for
diverse
types.
Graphical
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Апрель 18, 2023
Abstract
AlphaFold2
(AF2)
provides
structures
for
every
protein,
opening
up
prospects
virtually
field
in
structural
biology.
However,
transmembrane
proteins
pose
a
challenge
experimental
scientists,
resulting
limited
number
of
solved
structures.
Consequently,
algorithms
trained
on
this
finite
training
set
also
face
difficulties.
To
address
issue,
we
recently
launched
the
TmAlphaFold
database,
where
predicted
are
embedded
into
membrane
and
quality
assessment
is
provided
each
prediction
using
geometrical
evaluation.
In
paper,
analyze
how
AF2
has
changed
coverage
compared
to
earlier
years
when
only
were
available,
high-throughput
structure
was
greatly
limited.
We
evaluate
can
be
used
search
(distant)
homologs
highly
diverse
protein
families.
By
combining
homology
search,
pinpoint
families
accuracy
limited,
approaches
still
desired.
Proteoglycan Research,
Год журнала:
2023,
Номер
1(3)
Опубликована: Июль 1, 2023
Abstract
We
have
previously
shown
that
the
extracellular
domains
of
four
syndecans
are
intrinsically
disordered,
and
adopt
a
wide
range
conformations.
report
here
building
coarse‐grained
models
human
2
4
using
small‐angle
X‐ray
scattering
restraints.
One,
two
or
three
heparan
sulfate
(HS)
hexadecasaccharides,
(IdoA[2S]GlcNS[6S])
8
,
were
attached
to
serine
residues
core
proteins,
resulting
in
eight
variants
for
each
syndecan
used
all‐atom
molecular
dynamics
(MD)
simulations
(0.5–1
µs).
Syndecan‐4
had
larger
conformational
diversity
than
syndecan‐2,
remained
extended
during
MD
absence
HS
whereas
syndecan‐2
adopted
more
compact
Their
proteins
thus
appeared
be
structurally
distinct.
The
chains
also
behave
differently,
middle
chain
being
flexible
syndecan‐4,
third
able
interact
with
protein
regions
mediating
cell
adhesion.
adhesion
sites
on
both
flexible,
without
chains,
NXIP
motif
located
particularly
region.
In
conclusion,
induce
moderate
changes
syndecans,
depending
number
their
location
protein,
itself.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 15, 2024
Abstract
Tissue
maintenance
is
underpinned
by
resident
stem
cells
whose
activity
modulated
microenvironmental
cues.
Using
Drosophila
as
a
simple
model
to
identify
regulators
of
cell
behaviour
and
survival
in
vivo
,
we
have
identified
novel
connections
between
the
conserved
transmembrane
proteoglycan
Syndecan,
nuclear
properties
function.
In
midgut,
Syndecan
depletion
intestinal
results
their
loss
from
tissue,
impairing
tissue
renewal.
At
cellular
level,
alters
shape,
causes
lamina
invaginations
DNA
damage.
second
developing
brain,
live
imaging
revealed
that
neural
envelope
remodelling
defects
which
arise
upon
division.
Our
findings
reveal
new
role
for
diverse
types.
Graphical