Nucleic Acids Research,
Год журнала:
2024,
Номер
52(4), С. 2012 - 2029
Опубликована: Янв. 15, 2024
In
both
prokaryotic
and
eukaryotic
innate
immune
systems,
TIR
domains
function
as
NADases
that
degrade
the
key
metabolite
NAD+
or
generate
signaling
molecules.
Catalytic
activation
of
requires
oligomerization,
but
how
this
is
achieved
varies
in
distinct
systems.
Short
Argonaute
(pAgo)/TIR-APAZ
(SPARTA)
system,
NADase
activity
triggered
upon
guide
RNA-mediated
recognition
invading
DNA
by
an
unknown
mechanism.
Here,
we
describe
cryo-EM
structures
SPARTA
inactive
monomeric
target
DNA-activated
tetrameric
states.
The
structure
reveals
absence
DNA,
a
C-terminal
tail
TIR-APAZ
occupies
nucleic
acid
binding
cleft
formed
pAgo
subunits,
inhibiting
activation.
active
complex,
displaces
induces
conformational
changes
facilitate
SPARTA-SPARTA
dimerization.
Concurrent
release
rotation
one
domain
allow
it
to
form
composite
catalytic
site
with
other
within
dimer,
self-complementary
interface
mediates
cooperative
tetramerization.
Combined,
study
provides
critical
insights
into
structural
architecture
molecular
mechanism
underlying
DNA-dependent
oligomerization
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Янв. 11, 2024
Argonaute
(Ago)
proteins
are
ubiquitous
across
all
kingdoms
of
life.
Eukaryotic
Agos
(eAgos)
use
small
RNAs
to
recognize
transcripts
for
RNA
silencing
in
eukaryotes.
In
contrast,
the
functions
prokaryotic
counterparts
(pAgo)
less
well
known.
Recently,
short
pAgos
conjunction
with
associated
TIR
or
Sir2
(SPARTA
SPARSA)
were
found
serve
as
antiviral
systems
combat
phage
infections.
Herein,
we
present
cryo-EM
structures
nicotinamide
adenine
dinucleotide
(NAD
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Март 27, 2024
Abstract
The
Silent
Information
Regulator
2
(SIR2)
protein
is
widely
implicated
in
antiviral
response
by
depleting
the
cellular
metabolite
NAD
+
.
defense-associated
sirtuin
(DSR2)
effector,
a
SIR2
domain-containing
protein,
protects
bacteria
from
phage
infection
,
while
an
anti-DSR2
(DSR
anti-defense
1,
DSAD1)
employed
some
phages
to
evade
this
host
defense.
NADase
activity
of
DSR2
unleashed
recognizing
tail
tube
(TTP).
However,
activation
and
inhibition
mechanisms
are
unclear.
Here,
we
determine
cryo-EM
structures
multiple
states.
arranged
as
dimer
dimers,
which
facilitated
tetramerization
domains.
Moreover,
assembly
essential
for
activating
function.
activator
TTP
binding
would
trigger
opening
catalytic
pocket
decoupling
N-terminal
domain
C-terminal
(CTD)
DSR2.
Importantly,
further
show
that
mechanism
conserved
among
other
SIR2-dependent
anti-phage
systems.
Interestingly,
inhibitor
DSAD1
mimics
trap
DSR2,
thus
occupying
TTP-binding
inhibiting
Together,
our
results
provide
molecular
insights
into
regulatory
depletion
immunity.
Cell Host & Microbe,
Год журнала:
2024,
Номер
32(4), С. 453 - 465.e6
Опубликована: Март 20, 2024
The
plant
homolog
of
vertebrate
necroptosis
inducer
mixed-lineage
kinase
domain-like
(MLKL)
contributes
to
downstream
steps
in
Toll-interleukin-1
receptor
domain
NLR
(TNL)-receptor-triggered
immunity.
Here,
we
show
that
Arabidopsis
MLKL1
(AtMLKL1)
clusters
into
puncta
at
the
plasma
membrane
upon
TNL
activation
and
this
sub-cellular
reorganization
is
dependent
on
signal
transducer,
EDS1.
We
find
AtMLKLs
confer
TNL-triggered
immunity
parallel
with
RPW8-type
HeLo-domain-containing
NLRs
(RNLs)
AtMLKL
N-terminal
HeLo
indispensable
for
both
clustering.
mediates
cytoplasmic
Ca
Nucleic Acids Research,
Год журнала:
2024,
Номер
52(4), С. 2012 - 2029
Опубликована: Янв. 15, 2024
In
both
prokaryotic
and
eukaryotic
innate
immune
systems,
TIR
domains
function
as
NADases
that
degrade
the
key
metabolite
NAD+
or
generate
signaling
molecules.
Catalytic
activation
of
requires
oligomerization,
but
how
this
is
achieved
varies
in
distinct
systems.
Short
Argonaute
(pAgo)/TIR-APAZ
(SPARTA)
system,
NADase
activity
triggered
upon
guide
RNA-mediated
recognition
invading
DNA
by
an
unknown
mechanism.
Here,
we
describe
cryo-EM
structures
SPARTA
inactive
monomeric
target
DNA-activated
tetrameric
states.
The
structure
reveals
absence
DNA,
a
C-terminal
tail
TIR-APAZ
occupies
nucleic
acid
binding
cleft
formed
pAgo
subunits,
inhibiting
activation.
active
complex,
displaces
induces
conformational
changes
facilitate
SPARTA-SPARTA
dimerization.
Concurrent
release
rotation
one
domain
allow
it
to
form
composite
catalytic
site
with
other
within
dimer,
self-complementary
interface
mediates
cooperative
tetramerization.
Combined,
study
provides
critical
insights
into
structural
architecture
molecular
mechanism
underlying
DNA-dependent
oligomerization
