Legionella
pneumophila
causes
a
severe
pneumonia
known
as
Legionnaires'
disease.
During
the
infection,
injects
more
than
300
effector
proteins
into
host
cells.
Among
them
are
enzymes
involved
in
altering
host-ubiquitination
system.
Here,
we
identified
two
LegionellaOTU
(ovarian
tumor)-like
deubiquitinases
(LOT-DUBs;
LotB
[Lpg1621/Ceg23]
and
LotC
[Lpg2529]).
The
crystal
structure
of
catalytic
core
(LotC14-310)
was
determined
at
2.4
Å.
Unlike
classical
OTU-family,
LOT-family
shows
an
extended
helical
lobe
between
Cys-loop
variable
loop,
which
defines
unique
class
OTU-DUBs.
has
additional
ubiquitin-binding
site
(S1'),
enables
specific
cleavage
Lys63-linked
polyubiquitin
chains.
By
contrast,
only
contains
S1
cleaves
different
species
ubiquitin
MS
analysis
categories
host-interacting
substrates.
Together,
our
results
provide
new
structural
insights
bacterial
OTU-DUBs
indicate
distinct
roles
host-pathogen
interactions.
Annual Review of Microbiology,
Journal Year:
2022,
Volume and Issue:
76(1), P. 211 - 233
Published: Sept. 8, 2022
Ubiquitination
is
a
posttranslational
modification
that
regulates
multitude
of
cellular
functions.
Pathogens,
such
as
bacteria
and
viruses,
have
evolved
sophisticated
mechanisms
evade
or
counteract
ubiquitin-dependent
host
responses,
even
exploit
the
ubiquitin
system
to
their
own
advantage.
This
largely
done
by
numerous
pathogen
virulence
factors
encode
E3
ligases
deubiquitinases,
which
are
often
used
weapons
in
pathogen–host
cell
interactions.
Moreover,
upon
attack,
signaling
networks
undergo
major
changes
protect
cell,
including
coordination
innate
immunity,
remodeling
organelles,
reorganization
cytoskeleton,
reprogramming
metabolic
pathways
restrict
growth
pathogen.
Here
we
provide
mechanistic
insights
into
regulation
host-pathogen
interactions
how
it
affects
bacterial
viral
pathogenesis
organization
response
cell.
Biochemical Society Transactions,
Journal Year:
2019,
Volume and Issue:
47(6), P. 1857 - 1866
Published: Dec. 17, 2019
Protein
ubiquitination
is
a
posttranslational
modification
that
regulates
many
aspects
of
cellular
life,
including
proteostasis,
vesicular
trafficking,
DNA
repair
and
NF-κB
activation.
By
directly
targeting
intracellular
bacteria
or
bacteria-containing
vacuoles
to
the
lysosome,
also
an
important
component
cell-autonomous
immunity.
Not
surprisingly,
several
pathogenic
encode
deubiquitinases
(DUBs)
use
them
as
secreted
effectors
prevent
bacterial
components.
A
systematic
overview
known
DUBs,
their
cleavage
specificities
biological
roles,
suggests
multiple
independent
acquisition
events
from
host-encoded
DUBs
other
proteases.
The
widely
used
classification
into
seven
well-defined
families
should
only
be
applied
eukaryotic
since
do
not
follow
this
classification.
Legionella
pneumophila
causes
a
severe
pneumonia
known
as
Legionnaires'
disease.
During
the
infection,
injects
more
than
300
effector
proteins
into
host
cells.
Among
them
are
enzymes
involved
in
altering
host-ubiquitination
system.
Here,
we
identified
two
LegionellaOTU
(ovarian
tumor)-like
deubiquitinases
(LOT-DUBs;
LotB
[Lpg1621/Ceg23]
and
LotC
[Lpg2529]).
The
crystal
structure
of
catalytic
core
(LotC14-310)
was
determined
at
2.4
Å.
Unlike
classical
OTU-family,
LOT-family
shows
an
extended
helical
lobe
between
Cys-loop
variable
loop,
which
defines
unique
class
OTU-DUBs.
has
additional
ubiquitin-binding
site
(S1'),
enables
specific
cleavage
Lys63-linked
polyubiquitin
chains.
By
contrast,
only
contains
S1
cleaves
different
species
ubiquitin
MS
analysis
categories
host-interacting
substrates.
Together,
our
results
provide
new
structural
insights
bacterial
OTU-DUBs
indicate
distinct
roles
host-pathogen
interactions.
