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Multiple Orientia tsutsugamushi ankyrin repeat proteins interact with SCF1 ubiquitin ligase complex and eukaryotic elongation factor 1 α.
[scrub typhus]
Orientia
tsutsugamushi
,
the
causative
agent
of
scrub
typhus
,
is
an
obligate
intracellular
bacterium
.
Previously
,
a
large
number
of
genes
that
encode
proteins
containing
eukaryotic
protein-protein
interaction
motifs
such
as
ankyrin-repeat
(
Ank
)
domains
were
identified
in
the
O
.
tsutsugamushi
genome
.
However
,
little
is
known
about
the
Ank
protein
function
in
O
.
tsutsugamushi
.
To
characterize
the
function
of
Ank
proteins
,
we
investigated
a
group
of
Ank
proteins
containing
an
F-
box-like
domain
in
the
C-
terminus
in
addition
to
the
Ank
domains
.
All
nine
selected
ank
genes
were
expressed
at
the
transcriptional
level
in
host
cells
infected
with
O
.
tsutsugamushi
,
and
specific
antibody
responses
against
three
Ank
proteins
were
detected
in
the
serum
from
human
patients
,
indicating
an
active
expression
of
the
bacterial
Ank
proteins
post
infection
.
When
ectopically
expressed
in
HeLa
cells
,
the
Ank
proteins
of
O
.
tsutsugamushi
were
consistently
found
in
the
nucleus
and
/
or
cytoplasm
.
In
GST
pull-down
assays
,
multiple
Ank
proteins
specifically
interacted
with
Cullin
1
and
Skp
1
,
core
components
of
the
SCF
1
ubiquitin
ligase
complex
,
as
well
as
the
eukaryotic
elongation
factor
1
α
(
EF
1
α
)
.
Moreover
,
one
Ank
protein
co
-
localized
with
the
identified
host
targets
and
induced
downregulation
of
EF
1
α
potentially
via
enhanced
ubiquitination
.
The
downregulation
of
EF
1
α
was
observed
consistently
in
diverse
host
cell
types
infected
with
O
.
tsutsugamushi
.
These
results
suggest
that
conserved
targeting
and
subsequent
degradation
of
EF
1
α
by
multiple
O
.
tsutsugamushi
Ank
proteins
could
be
a
novel
bacterial
strategy
for
replication
and
/
or
pathogenesis
during
mammalian
host
infection
.
Diseases
Validation
Diseases presenting
"eukaryotic protein-protein interaction motifs"
symptom
scrub typhus
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