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
Molecular Plant,
Год журнала:
2022,
Номер
16(1), С. 75 - 95
Опубликована: Ноя. 22, 2022
To
counter
pathogen
invasion,
plants
have
evolved
a
large
number
of
immune
receptors,
including
membrane-resident
pattern
recognition
receptors
(PRRs)
and
intracellular
nucleotide-binding
leucine-rich
repeat
(NLRs).
Our
knowledge
about
PRR
NLR
signaling
mechanisms
has
expanded
significantly
over
the
past
few
years.
Plant
NLRs
form
multi-protein
complexes
called
resistosomes
in
response
to
effectors,
mediated
by
converges
on
Ca2+-permeable
channels.
channels
important
for
also
been
identified.
These
findings
highlight
crucial
role
Ca2+
triggering
plant
signaling.
In
this
review,
we
first
discuss
structural
biochemical
non-canonical
then
summarize
our
immune-related
their
roles
We
potential
intricate
interaction
between
Cell Research,
Год журнала:
2023,
Номер
33(9), С. 699 - 711
Опубликована: Июнь 13, 2023
Nicotinamide
adenine
dinucleotide
(NAD+)
is
a
central
metabolite
in
cellular
processes.
Depletion
of
NAD+
has
been
demonstrated
to
be
prevalent
theme
both
prokaryotic
and
eukaryotic
immune
responses.
Short
Argonaute
proteins
(Agos)
are
associated
with
NADase
domain-containing
(TIR-APAZ
or
SIR2-APAZ)
encoded
the
same
operon.
They
confer
immunity
against
mobile
genetic
elements,
such
as
bacteriophages
plasmids,
by
inducing
depletion
upon
recognition
target
nucleic
acids.
However,
molecular
mechanisms
underlying
activation
NADase/Ago
systems
remain
unknown.
Here,
we
report
multiple
cryo-EM
structures
complexes
from
two
distinct
(TIR-APAZ/Ago
SIR2-APAZ/Ago).
Target
DNA
binding
triggers
tetramerization
TIR-APAZ/Ago
complex
cooperative
self-assembly
mechanism,
while
heterodimeric
SIR2-APAZ/Ago
does
not
assemble
into
higher-order
oligomers
binding.
activities
these
unleashed
via
similar
closed-to-open
transition
catalytic
pocket,
albeit
different
mechanisms.
Furthermore,
functionally
conserved
sensor
loop
employed
inspect
guide
RNA-target
base
pairing
facilitate
conformational
rearrangement
Ago
required
for
systems.
Overall,
our
study
reveals
mechanistic
diversity
similarity
protein-associated
response.
Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(7)
Опубликована: Фев. 8, 2023
Nicotinamide
adenine
dinucleotide
(NAD
+
)
has
emerged
as
a
key
component
in
prokaryotic
and
eukaryotic
immune
systems.
The
recent
discovery
that
Toll/interleukin-1
receptor
(TIR)
proteins
function
NAD
hydrolases
(NADase)
links
-derived
small
molecules
with
signaling.
We
investigated
pathogen
manipulation
of
host
metabolism
virulence
strategy.
Using
the
pangenome
model
bacterial
Pseudomonas
syringae
,
we
conducted
structure-based
similarity
search
from
35,000
orthogroups
for
type
III
effectors
(T3Es)
potential
NADase
activity.
Thirteen
T3Es,
including
five
newly
identified
candidates,
were
possess
domain(s)
characteristic
seven
-hydrolyzing
enzyme
families.
Most
strains
depend
on
secretion
system
to
cause
disease,
encode
at
least
one
-manipulating
T3E,
many
have
several.
experimentally
confirmed
III-dependent
novel
named
HopBY,
which
shows
structural
both
TIR
adenosine
diphosphate
ribose
(ADPR)
cyclase.
Homologs
HopBY
predicted
be
VI
diverse
species,
indicating
recruitment
this
activity
by
microbial
secreted
during
various
interspecies
interactions.
efficiently
hydrolyzes
specifically
produces
2′cADPR,
can
also
produced
receptors
plants
other
bacteria.
Intriguingly,
effector
promoted
virulence,
2′cADPR
may
not
signaling
molecule
directly
initiates
immunity.
This
study
highlights
host-pathogen
battleground
centered
around
provides
insight
into
involved
plant
Annual Review of Biophysics,
Год журнала:
2023,
Номер
52(1), С. 207 - 228
Опубликована: Янв. 10, 2023
Nucleotide-binding
and
leucine-rich
repeat
(NLR)
proteins
are
critical
intracellular
immune
receptors
in
both
animals
plants.
Perception
of
pathogen-derived
or
stress-associated
signals
induces
NLR
oligomerization
to
form
multiprotein
complexes
called
inflammasomes
resistosomes
plants
mediate
host
response.
Significant
progress
has
been
made
during
the
past
few
years
our
understanding
biology,
particularly
structural
perspective
these
two
types
NLR-containing
complexes.
In
this
article,
we
review
latest
advances
knowledge
how
activated
assembled
information
provides
insight
into
their
distinct
mechanisms
action.
Commonalities
differences
between
also
discussed.
Current Opinion in Plant Biology,
Год журнала:
2023,
Номер
74, С. 102373 - 102373
Опубликована: Май 5, 2023
Toll/interleukin-1/resistance
(TIR)
domain
proteins
contribute
to
innate
immunity
in
all
cellular
kingdoms.
TIR
modules
are
activated
by
self-association
and
plants,
mammals
bacteria,
some
TIRs
have
enzymatic
functions
that
crucial
for
disease
resistance
and/or
cell
death.
Many
plant
TIR-only
pathogen
effector-activated
TIR-domain
NLR
receptors
NAD+
hydrolysing
enzymes.
Biochemical,
structural
functional
studies
established
both
TIR-protein
types,
certain
bacterial
TIRs,
NADase
activity
generates
bioactive
signalling
intermediates
which
promote
resistance.
A
set
of
TIR-catalysed
nucleotide
isomers
was
discovered
bind
activate
EDS1
complexes,
promoting
their
interactions
with
co-functioning
helper
NLRs.
Analysis
enzymes
across
kingdoms
fills
an
important
gap
understanding
how
disturbance
induces
TIR-regulated
immune
responses.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 3, 2024
Abstract
TIR
domains
are
central
components
of
pattern
recognition
immune
proteins
across
all
life.
In
both
bacteria
and
plants,
TIR-domain
were
shown
to
recognize
pathogen
invasion
then
produce
signaling
molecules
exclusively
comprising
nucleotide
moieties.
Here
we
show
that
the
domain
protein
type
II
Thoeris
defense
system
in
produces
a
unique
molecule
amino
acid
histidine
conjugated
ADP-ribose
(His-ADPR).
His-ADPR
is
generated
response
phage
infection
activates
cognate
effector
by
binding
Macro
located
at
C-terminus
protein.
By
determining
crystal
structure
ligand-bound
domain,
describe
structural
basis
for
recognition.
Our
analyses
furthermore
reveal
family
bind
sequester
molecules,
allowing
phages
evade
TIR-
mediated
immunity.
These
data
demonstrate
diversity
bacterial
new
class
TIR-derived
combining