Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Nov. 22, 2023
Deubiquitinating
enzymes
(DUBs)
are
emerging
as
key
factors
for
the
infection
of
human
cells
by
pathogens
such
bacteria
and
parasites.
In
this
review,
we
discuss
most
recent
studies
on
role
deubiquitinase
activity
in
exploiting
manipulating
ubiquitin
(Ub)-dependent
host
processes
during
infection.
The
discussed
here
highlight
importance
DUB
host-pathogen
research
underscore
therapeutic
potential
inhibiting
pathogen-specific
to
prevent
infectious
diseases.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 15, 2024
Abstract
The
intracellular
bacterial
pathogen
Legionella
pneumophila
modulates
host
cell
functions
by
secreting
multiple
effectors
with
diverse
biochemical
activities.
In
particular,
of
the
SidE
family
interfere
protein
ubiquitination
in
a
process
that
involves
production
phosphoribosyl
ubiquitin
(PR-Ub).
Here,
we
show
effector
LnaB
converts
PR-Ub
into
ADP-ribosylated
ubiquitin,
which
is
further
processed
to
ADP-ribose
and
functional
(ADP-ribosyl)hydrolase
MavL,
thus
maintaining
homeostasis
infected
cells.
Upon
being
activated
actin,
also
undergoes
self-AMPylation
on
tyrosine
residues.
activity
requires
motif
consisting
Ser,
His
Glu
(SHxxxE)
present
large
toxins
from
pathogens.
Thus,
our
study
sheds
light
mechanisms
maintains
identifies
enzymes
capable
AMPylation.
Microbiology,
Journal Year:
2022,
Volume and Issue:
168(5)
Published: May 23, 2022
To
prevail
in
the
interaction
with
eukaryotic
hosts,
many
bacterial
pathogens
use
protein
secretion
systems
to
release
virulence
factors
at
host–pathogen
interface
and/or
deliver
them
directly
into
host
cells.
An
outstanding
example
of
complexity
and
sophistication
diversity
their
substrates,
effectors,
is
Defective
organelle
trafficking/Intracellular
multiplication
(Dot/Icm)
Type
IVB
system
(T4BSS)
Legionella
pneumophila
related
species.
species
are
facultative
intracellular
environmental
protozoa
opportunistic
human
respiratory
pathogens.
The
Dot/Icm
T4BSS
translocates
an
exceptionally
large
number
more
than
300
per
L.
strain,
essential
for
evasion
phagolysosomal
degradation
exploitation
macrophages
as
replicative
niches.
Recent
technological
advancements
imaging
complexes
have
provided
new
insight
architecture
allowed
us
propose
models
transport
mechanism.
At
same
time,
significant
progress
has
been
made
assigning
functions
about
a
third
discovering
unprecedented
enzymatic
activities
concepts
subversion.
In
this
review,
we
describe
current
knowledge
workings
machinery
provide
overview
to-date
characterized
effectors
Seminars in Cell and Developmental Biology,
Journal Year:
2022,
Volume and Issue:
132, P. 230 - 241
Published: Feb. 15, 2022
Legionella
pneumophila,
a
Gram-negative
intracellular
bacterium,
is
one
of
the
major
causes
Legionnaires'
disease,
specific
type
atypical
pneumonia.
Despite
intensive
research
efforts
that
elucidated
many
relevant
structural,
molecular
and
medical
insights
into
Legionella's
pathogenicity,
disease
continues
to
present
an
ongoing
public
health
concern.
virulence
based
on
its
ability
simultaneously
hijack
multiple
pathways
host
cell
ensure
fast
replication
dissemination.
usurps
ubiquitin
system
through
effector
proteins,
using
advantage
both
conventional
unconventional
(phosphoribosyl-linked)
ubiquitination,
thus
providing
optimal
conditions
for
replication.
In
this
review,
we
summarize
current
understanding
L.
pneumophila
from
medical,
biochemical
perspectives.
We
describe
clinical
presentation,
diagnostics
treatment,
as
well
host-pathogen
interactions,
with
emphasis
target
upon
infection.
Furthermore,
interdisciplinary
use
innovative
technologies
enables
better
pathogenesis
provides
new
opportunities
treatment
prevention.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: March 19, 2024
Abstract
ADP-ribosylation
is
a
reversible
post-translational
modification
involved
in
various
cellular
activities.
Removal
of
requires
(ADP-ribosyl)hydrolases,
with
macrodomain
enzymes
being
major
family
this
category.
The
pathogen
Legionella
pneumophila
mediates
atypical
ubiquitination
host
targets
using
the
SidE
effector
process
that
involves
ubiquitin
on
arginine
42
as
an
obligatory
step.
Here,
we
show
MavL
regulates
pathway
by
reversing
ADP-ribosylation,
likely
to
minimize
potential
detrimental
effects
caused
modified
ubiquitin.
We
determine
crystal
structure
ADP-ribose-bound
MavL,
providing
structural
insights
into
recognition
ADP-ribosyl
group
and
catalytic
mechanism
its
removal.
Further
analyses
reveal
DUF4804
class
MavL-like
whose
representative
members
unique
selectivity
for
mono-ADP-ribosylated
residue
synthetic
substrates.
find
such
are
also
present
eukaryotes,
exemplified
two
previously
uncharacterized
(ADP-ribosyl)hydrolases
Drosophila
melanogaster
.
Crystal
structures
several
proteins
provide
specificity
shared
mode
ADP-ribose
interaction
distinct
from
characterized
macrodomains.
Collectively,
our
study
reveals
new
regulatory
layer
SidE-catalyzed
expands
current
understanding
enzymes.
Autophagy,
Journal Year:
2024,
Volume and Issue:
20(9), P. 1968 - 1983
Published: May 31, 2024
Many
bacterial
pathogens
have
evolved
effective
strategies
to
interfere
with
the
ubiquitination
network
evade
clearance
by
innate
immune
system.
Here,
we
report
that
OTUB1,
one
of
most
abundant
deubiquitinases
(DUBs)
in
mammalian
cells,
is
subjected
both
canonical
and
noncanonical
during
Legionella
pneumophila
infection.
The
effectors
SidC
SdcA
catalyze
OTUB1
at
multiple
lysine
residues,
resulting
its
association
a
Legionella-containing
vacuole.
Lysine
promotes
interactions
between
DEPTOR,
an
inhibitor
MTORC1
pathway,
thus
suppressing
signaling.
inhibition
leads
suppression
host
protein
synthesis
promotion
macroautophagy/autophagy
L.
In
addition,
members
SidE
family
(SidEs)
induce
phosphoribosyl
(PR)-linked
Ser16
Ser18
block
DUB
activity.
levels
serine
are
further
regulated
function
antagonize
activities
SidC,
SidEs,
including
Lem27,
DupA,
DupB,
SidJ
SdjA.
Our
study
reveals
effectors-mediated
complicated
mechanism
regulating
activity
DUB.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 30, 2024
Ubiquitination
is
a
posttranslational
modification
in
eukaryotes
that
plays
significant
role
the
infection
of
intracellular
microbial
pathogens,
such
as
Legionella
pneumophila.
While
Legionella-containing
vacuole
(LCV)
coated
with
ubiquitin
(Ub),
it
avoids
recognition
by
autophagy
adaptors.
Here,
we
report
Sdc
and
Sde
families
effectors
work
together
to
build
ubiquitinated
species
around
LCV.
The
catalyze
canonical
polyubiquitination
directly
on
host
targets
or
phosphoribosyl-Ub
conjugated
Sde.
Remarkably,
Ub
moieties
within
poly-Ub
chains
are
either
modified
phosphoribosyl
group
PDE
domain-containing
covalently
attached
other
substrates
via
Sde-mediated
phosphoribosyl-ubiquitination.
Furthermore,
these
modifications
prevent
adaptors
therefore
exclude
from
In
this
work,
shed
light
nature
poly-ubiquitinated
present
at
surface
LCV
provide
molecular
mechanism
for
avoidance
Ub-decorated
Frontiers in Cellular and Infection Microbiology,
Journal Year:
2020,
Volume and Issue:
10
Published: Aug. 21, 2020
The
intracellular
bacterial
pathogen
Legionella
pneumophila
employs
bacteria-derived
effector
proteins
in
a
variety
of
functions
to
exploit
host
cellular
systems.
ubiquitination
machinery
constitutes
crucial
eukaryotic
system
for
the
regulation
numerous
processes
and
is
representative
target
effector-mediated
manipulation.
L.
transports
more
than
300
into
cells
through
type
IV
secretion
system.
Among
these,
several
have
been
found
function
as
ubiquitin
ligases,
including
unprecedented
enzymes
that
catalyze
unconventional
mechanisms.
Recent
studies
identified
many
can
interfere
ubiquitination.
These
effectors
include
are
distantly
related
ovarian
tumor
protein
superfamily
described
deubiquitinases
(DUBs),
which
regulate
important
signaling
cascades
human
cells.
Intriguingly,
DUBs
not
limited
exhibit
canonical
DUB
activity.
Some
cleavage
linkage
substrates.
Furthermore,
novel
mechanisms
adversely
affect
specific
ligases;
instance,
an
posttranslational
modification
ligases
results
inhibition
their
Bacterial
inhibit
ligase
activity,
cognate
DUBs,
examples
effector/metaeffector
sets
due
opposing
functional
relationship.
In
context
infection,
existence
reverse
mainly
relates
fine
tuning
biogenesis
remodeling
Legionella-containing
vacuole
replicative
niche.
complexity
arrays
reflects
sophisticated
strategies
bacteria
adopted
adapt
its
environment
enable
survival
This
review
summarizes
current
state
knowledge
on
divergent
ubiquitination,
mediated
by
other
well
machinery.