RSC Chemical Biology,
Journal Year:
2021,
Volume and Issue:
2(5), P. 1509 - 1519
Published: Jan. 1, 2021
Legionella
pneumophila
establishes
a
replication
vacuole
by
translocating
hundreds
of
protein
effectors
through
type
IV
secretion
system
(T4SS).
Among
these
translocated
are
members
the
Sde
family,
which
catalyze
phosphoribosyl-linked
ubiquitination
(pR-Ub)
host
targets.
Previous
work
has
posited
that
proteins
solely
target
serine
(Ser)
residues
within
acceptor
substrates.
We
show
here
SdeC-mediated
pR-Ub
modification
results
from
stepwise
reaction
also
modifies
tyrosine
(Tyr)
residues.
Unexpectedly,
presence
an
HA
tag
on
Ub
resulted
in
poly-pR-ubiquitination,
consistent
with
acting
as
target.
Interrogation
HA-Ub
revealed
Tyr4
was
preferred
targeted
residue,
based
LC-MS/MS
analysis
crosslinked
product.
Further
using
synthetic
variants
promiscuous
Tyr,
crosslinking
prevented
only
constructing
triple
mutant
all
three
Tyr
sequence
were
substituted
Phe.
Although
previous
indicated
Ser
is
sole
we
found
no
evidence
preference
over
→
replacement
mutants.
This
demonstrates
pR-ubiquitination
family
not
limited
to
Ser-modification
previously
proposed,
and
broadens
potential
sites
this
family.
Protein & Cell,
Journal Year:
2023,
Volume and Issue:
15(3), P. 157 - 190
Published: July 19, 2023
Ubiquitination/ubiquitylation,
one
of
the
most
fundamental
post-translational
modifications,
regulates
almost
every
critical
cellular
process
in
eukaryotes.
Emerging
evidence
has
shown
that
essential
components
numerous
biological
processes
undergo
ubiquitination
mammalian
cells
upon
exposure
to
diverse
stresses,
from
exogenous
factors
reactions,
causing
a
dazzling
variety
functional
consequences.
Various
forms
ubiquitin
signals
generated
by
ubiquitylation
events
specific
milieus,
known
as
codes,
constitute
an
intrinsic
part
myriad
stress
responses.
These
events,
leading
proteolytic
turnover
substrates
or
just
switch
functionality,
initiate,
regulate,
supervise
multiple
stress-associated
responses,
supporting
adaptation,
homeostasis
recovery,
and
survival
stressed
cells.
In
this
review,
we
attempted
summarize
crucial
roles
response
different
environmental
intracellular
while
discussing
how
stresses
modulate
system.
This
review
also
updates
recent
advances
understanding
machinery
well
responses
discusses
some
important
questions
may
warrant
future
investigation.
Frontiers in Molecular Biosciences,
Journal Year:
2022,
Volume and Issue:
9
Published: Sept. 19, 2022
The
post-translational
modification
of
proteins
with
ubiquitin
plays
a
central
role
in
nearly
all
aspects
eukaryotic
biology.
Historically,
studies
have
focused
on
the
conjugation
to
lysine
residues
substrates,
but
it
is
now
clear
that
ubiquitylation
can
also
occur
cysteine,
serine,
and
threonine
residues,
as
well
N-terminal
amino
group
proteins.
Paradigm-shifting
reports
non-proteinaceous
substrates
further
extended
reach
beyond
proteome
include
intracellular
lipids
sugars.
Additionally,
results
from
bacteria
revealed
novel
ways
ubiquitylate
(and
deubiquitylate)
without
need
for
any
enzymatic
components
canonical
cascade.
Focusing
mainly
upon
recent
findings,
this
review
aims
outline
current
understanding
non-lysine
speculate
molecular
mechanisms
physiological
importance
non-canonical
modification.
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.
Pseudokinases
are
considered
to
be
the
inactive
counterparts
of
conventional
protein
kinases
and
comprise
approximately
10%
human
mouse
kinomes.
Here,
we
report
crystal
structure
Legionella
pneumophila
effector
protein,
SidJ,
in
complex
with
eukaryotic
Ca2+-binding
regulator,
calmodulin
(CaM).
The
reveals
that
SidJ
contains
a
kinase-like
fold
domain,
which
retains
majority
characteristic
kinase
catalytic
motifs.
However,
fails
demonstrate
activity.
Instead,
mass
spectrometry
vitro
biochemical
analyses
modifies
another
SdeA,
an
unconventional
phosphoribosyl
ubiquitin
ligase,
by
adding
glutamate
molecules
specific
residue
SdeA
CaM-dependent
manner.
Furthermore,
show
SidJ-mediated
polyglutamylation
suppresses
ADP-ribosylation
Our
work
further
implies
some
pseudokinases
may
possess
ATP-dependent
activities
other
than
phosphorylation.
Cell Death and Differentiation,
Journal Year:
2021,
Volume and Issue:
28(2), P. 557 - 569
Published: Jan. 20, 2021
Abstract
Ubiquitination
is
an
essential
post-translational
modification
that
regulates
most
cellular
processes.
The
assembly
of
ubiquitin
into
polymeric
chains
by
E3
ligases
underlies
the
pleiotropic
functions
regulate.
Ubiquitin
assembled
via
N-terminal
methionine,
termed
Met1-linked
or
linear
chains,
have
emerged
as
signalling
scaffolds
regulate
pro-inflammatory
responses,
anti-viral
interferon
cell
death
and
xenophagy
bacterial
pathogens
downstream
innate
immune
receptors.
are
exclusively
chain
complex,
LUBAC,
disassembled
deubiquitinases
OTULIN
CYLD.
Genetic
defects
perturb
regulation
causes
severe
immune-related
disorders,
illustrating
their
potent
capacity.
Here,
we
review
current
knowledge
about
machinery
conjugates,
recognises,
disassembles
discuss
function
this
unique
posttranslational
in
regulating
inflammation,
immunity
to
pathogens.
Legionella
pneumophila
extensively
modulates
the
host
ubiquitin
network
to
create
Legionella-containing
vacuole
(LCV)
for
its
replication.
Many
of
virulence
factors
function
as
ligases
or
deubiquitinases
(DUBs).
Here,
we
identify
Lem27
a
DUB
that
displays
preference
diubiquitin
formed
by
K6,
K11,
K48.
is
associated
with
LCV
where
it
regulates
Rab10
ubiquitination
in
concert
SidC
and
SdcA,
two
bacterial
E3
ligases.
Structural
analysis
complex
an
active
fragment
substrate-based
suicide
inhibitor
ubiquitin-propargylamide
(PA)
reveals
harbors
fold
resembling
those
OTU1
subfamily
Cys-His
catalytic
dyad
recognizes
via
extensive
hydrogen
bonding
at
six
contact
sites.
Our
results
establish
functions
regulate
protein
on
L.
phagosomes
counteracting
activity
