Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Nov. 16, 2023
Abstract
Purines
and
their
derivatives
are
key
molecules
for
controlling
intracellular
energy
homeostasis
nucleotide
synthesis.
In
eukaryotes,
including
humans,
purines
also
act
as
signaling
that
mediate
extracellular
communication
control
cellular
processes,
such
proliferation,
migration,
differentiation,
apoptosis.
However,
the
role
of
in
bacteria
is
largely
unknown.
Here,
by
combining
structural
sequence
information,
we
define
a
purine-binding
motif,
which
present
sensor
domains
thousands
bacterial
receptors
modulate
motility,
gene
expression,
metabolism
second
messenger
turnover.
The
screening
compound
libraries
microcalorimetric
titrations
selected
validated
ability
to
specifically
bind
purine
derivatives.
physiological
relevance
sensing
was
demonstrated
system
modulates
c-di-GMP
levels.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 26, 2023
Abstract
Purines
and
their
derivatives
are
key
molecules
for
controlling
intracellular
energy
homeostasis
nucleotide
synthesis.
In
eukaryotes,
including
humans,
purines
also
act
as
signaling
that
mediate
extracellular
communication
control
cellular
processes,
such
proliferation,
migration,
differentiation,
apoptosis.
However,
the
role
of
in
bacteria
is
largely
unknown.
Here,
by
combining
structural
sequence
information,
we
define
a
purine-binding
motif,
which
present
sensor
domains
thousands
bacterial
receptors
modulate
motility,
gene
expression,
metabolism
second
messenger
turnover.
The
screening
compound
libraries
microcalorimetric
titrations
selected
validated
ability
to
specifically
bind
purine
derivatives.
physiological
relevance
sensing
was
demonstrated
system
modulates
c-di-GMP
levels.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 26, 2024
ABSTRACT
EAG1
depolarization-activated
potassium
selective
channels
are
important
targets
for
treatment
of
cancer
and
neurological
disorders.
formed
by
a
tetrameric
subunit
assembly
with
each
containing
an
N-terminal
Per-Arnt-Sim
(PAS)
domain
C-terminal
cyclic
nucleotide-binding
homology
(CNBH)
domain.
The
PAS
CNBH
domains
from
adjacent
subunits
interact
form
intracellular
ring
that
regulates
the
channel
gating,
including
movement
voltage
sensor
(VSD)
closed
to
open
states.
Small
molecule
ligands
can
inhibit
binding
their
domains.
However,
allosteric
pathways
this
inhibition
not
known.
Here
we
show
chlorpromazine,
small
binder,
alters
interactions
between
decreases
coupling
pore
channel,
while
having
little
effect
on
VSD
In
addition,
chlorpromazine
did
alter
Cole-Moore
shift
characteristic
channels,
further
indicating
has
no
deep
opened
Our
study
provides
framework
understanding
global
regulation
binders.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 21, 2024
Abstract
The
ubiquitous
second
messenger
cyclic
di-GMP
is
the
most
abundant
diffusible
nucleotide
signalling
system
in
bacteria
deciding
life
style
transition
between
sessility
and
motility.
GGDEF
diguanylate
cyclases
EAL
phosphodiesterases
conventionally
direct
turnover
of
this
signaling
molecule.
Thereby,
those
domains
are
subject
to
micro-
macroevolution
with
evolutionary
forces
that
promote
alterations
these
proteins
currently
mostly
unknown.
While
highly
conserved
signature
amino
acids
involved
divalent
ion
binding
catalysis
equally
as
signal
transduction
modules
have
been
readily
identified,
more
subtle
acid
substitutions
modulate
catalytic
activity
rarely
recognized
their
molecular
mechanism
characterized.
Our
previous
work
identified
A526V
substitution
be
downregulation
apparent
Zymomonas
mobilis
ZM4
PAS-GGDEF-EAL
ZMO1055
phosphodiesterase
leading
a
self-flocculation
phenotype
mediated
by
elevated
production
exopolysaccharide
cellulose
Z.
ZM401.
As
A526
located
at
position
has
previously
not
affect
domain,
we
further
investigated
mechanisms
functional
conservation
substitution.
Using
number
model
systems,
our
results
indicate
alanine
526
homologs
beyond
mutation
alter
subgroups
domains.
Thus
hypothesize
single
lead
amplify
output
thus
significantly
contribute
flexibility
adaptability
network.
In
context,
seems
current
target.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 3, 2024
Abstract
Light
response
is
a
fundamental
characteristic
of
eukaryotic
organisms,
both
unicellular
and
multicellular.
However,
no
photoresponse
has
previously
been
reported
in
Apusomonadida,
group
small,
free-living
biflagellates
phylogenetically
positioned
as
sister
to
Opisthokonta
(animals,
fungi,
their
relatives).
Apusomonads
are
thus
crucial
for
understanding
the
evolution
opisthokonts.
Here,
we
report
first
time
an
avoidance
blue
light
apusomonad
Podomonas
kaiyoae
.
This
accompanied
by
increase
gliding
velocity,
transient
changes
flagellar
waveforms,
alterations
cell
shape.
Dynamic
contraction
induced
intracellular
free
Ca2+
inhibited
either
dynein
inhibitor
or
actin-disrupting
drug.
These
findings
suggest
that
photophobic
behavior
relies
on
cytoskeletal
responses
mediated
dynein/tubulin
myosin/actin
systems,
which
were
acquired
early
evolution.
The
dominance
posterior
flagellum
cilia-driven
directional
further
supports
phylogenetic
placement
apusomonads
opisthokonts
rather
than
other
lineages.
