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A random Abstract
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VipD of Legionella pneumophila targets activated Rab5 and Rab22 to interfere with endosomal trafficking in macrophages.
[legionellosis]
Upon
phagocytosis
,
Legionella
pneumophila
translocates
numerous
effector
proteins
into
host
cells
to
perturb
cellular
metabolism
and
immunity
,
ultimately
establishing
intracellular
survival
and
growth
.
VipD
of
L
.
pneumophila
belongs
to
a
family
of
bacterial
effectors
that
contain
the
N-
terminal
lipase
domain
and
the
C-
terminal
domain
with
an
unknown
function
.
We
report
the
crystal
structure
of
VipD
and
show
that
its
C-
terminal
domain
robustly
interferes
with
endosomal
trafficking
through
tight
and
selective
interactions
with
Rab
5
and
Rab
22
.
This
domain
,
which
is
not
significantly
similar
to
any
known
protein
structure
,
potently
interacts
with
the
GTP-bound
active
form
of
the
two
Rabs
by
recognizing
a
hydrophobic
triad
conserved
in
Rabs
.
These
interactions
prevent
Rab
5
and
Rab
22
from
binding
to
downstream
effectors
Rabaptin-
5
,
Rabenosyn-
5
and
EEA
1
,
consequently
blocking
endosomal
trafficking
and
subsequent
lysosomal
degradation
of
endocytic
materials
in
macrophage
cells
.
Together
,
this
work
reveals
endosomal
trafficking
as
a
target
of
L
.
pneumophila
and
delineates
the
underlying
molecular
mechanism
.