bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 3, 2025
Summary
Nucleotide-binding
leucine-rich
repeat
receptors
(NLRs)
are
critical
in
plant
immunity
and
display
remarkable
allelic
diversity.
Coiled-coiled
NLRs
(CC-NLRs)
the
most
widespread
group
of
these
found
across
flowering
non-flowering
plants.
Here
we
investigate
sequence
conservation
functional
variation
conserved
EDVID
motif
α3-helix
cell
death
inducing
CC
domain
NLRs.
We
analyse
our
findings
context
published
protein
structures
structure
prediction.
find
that
can
serve
as
a
predictor
canonical
CC-NLR
function
oligomeric
assembly.
also
is
accompanied
by
preceding
acidic
residues
certain
CC-NLRs
with
homology
to
Arabidopsis
RPP8.
The
appearance
this
so-called
preEDVID
phylogeny
plants
its
contribution
underpins
structural
diversity
motif.
further
show
exist
have
lost
suggesting
subgroup,
previously
referred
G10
-NLRs,
functions
different
manner
from
mechanism.
located
helper
NLR
NRG1.1
linked
activity.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 9, 2024
Abstract
Sr50,
an
intracellular
nucleotide-binding
leucine-rich
repeat
receptor
(NLR),
confers
resistance
of
wheat
against
stem
rust
caused
by
the
fungal
pathogen
Puccinia
graminis
f.
sp.
tritici
.
The
recognizes
effector
AvrSr50
through
its
C-terminal
domain,
initiating
a
localized
cell
death
immune
response.
However,
this
immunity
is
compromised
mutations
in
effector,
as
escape
mutant
QCMJC
,
which
evades
Sr50
detection.
In
study,
we
employed
iterative
computational
structural
analyses
and
site-directed
mutagenesis
for
rational
engineering
to
gain
recognition
Following
initial
hypothesis
driven
molecular
docking,
identified
K711D
single
mutant,
induces
intermediate
response
without
losing
AvrSr50.
Increasing
gene
expression
with
stronger
promoter
enabled
elicit
robust
response,
indicating
weak
can
be
complemented
enhanced
expression.
Further
refinements
led
creation
five
double
mutants
two
triple
dual
greater
intensities
than
mutant.
All
effective
required
substitution,
that
multiple
solutions
exist
recognition,
but
path
reach
these
may
confined.
Furthermore,
substitution
alters
prediction
AlphaFold
2,
allowing
it
model
complex
structure
match
our
final
hypothesis.
Collectively,
study
outlines
framework
NLR
systems
overcome
provides
datasets
future
models
resurrection.
Plants,
Год журнала:
2025,
Номер
14(2), С. 278 - 278
Опубликована: Янв. 19, 2025
Plant
immunity
is
largely
governed
by
nucleotide-binding
leucine-rich
repeat
receptor
(NLR).
Here,
we
examine
the
molecular
activation
and
inhibition
mechanisms
of
wheat
CC-type
NLR
Yr10CG,
a
previously
proposed
candidate
for
Yr10
resistance
gene.
Though
recent
studies
have
identified
YrNAM
as
true
gene,
Yr10CG
remains
an
important
in
understanding
NLR-mediated
wheat.
In
this
study,
found
that
overexpression
either
full-length
or
its
CC
domain
Nicotiana
benthamiana
did
not
trigger
cell
death,
suggesting
robust
autoinhibitory
mechanism
within
Yr10CG.
However,
observed
mutations
conserved
MHD
motif,
specifically
D502G,
activated
induced
death.
Structural
modeling
indicated
mutation
disrupted
key
interactions
promoting
local
flexibility
activation.
We
further
explored
effector
recognition
potential
creating
chimeric
proteins
with
Sr50
domains,
revealing
both
NB-ARC
LRR
domains
are
necessary
recognition,
while
likely
functions
downstream
immune
signaling.
Additionally,
disrupting
membrane
localization
through
L11E
abolished
self-activation,
requirement
association
Our
findings
contribute
to
CC-NLR
autoinhibition
mechanisms,
highlighting
engineering
crop
improvement.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
ABSTRACT
Nucleotide-binding
domain
and
leucine-rich
repeat
immune
receptors
(NLRs)
are
known
for
their
rapid
evolution,
even
at
the
intraspecific
level,
yet
rates
of
evolution
differ
significantly
across
various
NLR
classes.
Within
NRC
(NLR
Required
Cell
Death)
network,
NLRs
operate
in
complex
sensor-helper
configurations
to
confer
immunity
against
a
diverse
array
pathogens,
particularly
Asterids.
While
helper
typically
conserved
evolve
slowly,
sensor
tend
more
rapidly.
However,
functional
connections
between
slow
fast-evolving
remain
poorly
understood,
notably
important
crop
species.
We
conducted
comparative
analysis
40
Solanales
29
Asterales
genomes
explore
network
expansion
diversification
within
less-studied
order.
Our
findings
reveal
that
has
expanded
less
compared
Solanales.
functionally
validated
minimal
with
2
helpers
9
sensors
common
lettuce
(
Lactuca
sativa
).
Through
selection
structural
modeling
subclades
genus,
we
found
varying
evolutionary
sensors.
correlation
dependency,
reliant
on
phylogenetically
experiencing
limited
pressure.
results
highlight
lineage-
function-specific
offering
insights
into
pressures
shaping
plant
receptor
networks.
PLoS Genetics,
Год журнала:
2025,
Номер
21(4), С. e1011653 - e1011653
Опубликована: Апрель 9, 2025
Parasites
can
counteract
host
immunity
by
suppressing
nucleotide
binding
and
leucine-rich
repeat
(NLR)
proteins
that
function
as
immune
receptors.
We
previously
showed
a
cyst
nematode
virulence
effector
SPRYSEC15
(SS15)
binds
inhibits
oligomerisation
of
helper
NLR
in
the
expanded
NRC1/2/3
clade
preventing
intramolecular
rearrangements
required
for
NRC
into
an
activated
resistosome.
Here
we
examined
degree
to
which
from
multiple
Solanaceae
species
are
sensitive
suppression
SS15
tested
hypotheses
about
adaptive
evolution
interface
between
inhibitor
proteins.
Whereas
all
orthologs
NRC2
were
inhibited
SS15,
some
natural
variants
NRC1
NRC3
insensitive
suppression.
Ancestral
sequence
reconstruction
combined
with
functional
assays
revealed
transitioned
ancestral
suppressed
form
one
over
19
million
years
ago.
Our
analyses
evolutionary
trajectory
receptor
against
parasite
inhibitor,
identifying
key
transitions
NLRs
this
inhibition.
This
work
reveals
distinct
type
gene-for-gene
interaction
or
pathogen
immunosuppressors
receptors
contrasts
coevolution
AVR
effectors
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(8), С. 3671 - 3671
Опубликована: Апрель 13, 2025
AlphaFold3,
the
latest
release
of
AlphaFold
developed
by
Google
DeepMind
and
Isomorphic
Labs,
was
designed
to
predict
protein
structures
with
remarkable
accuracy.
AlphaFold3
enhances
our
ability
model
not
only
single
but
also
complex
biomolecular
interactions,
including
protein–protein
protein–ligand
docking,
protein-nucleic
acid
complexes.
Herein,
we
provide
a
detailed
examination
AlphaFold3’s
capabilities,
emphasizing
its
applications
across
diverse
biological
fields
effectiveness
in
systems.
The
strengths
new
AI
are
highlighted,
dynamic
systems,
multi-chain
assemblies,
complicated
complexes
that
were
previously
challenging
depict.
We
explore
role
advancing
drug
discovery,
epitope
prediction,
study
disease-related
mutations.
Despite
significant
improvements,
present
review
addresses
ongoing
obstacles,
particularly
modeling
disordered
regions,
alternative
folds,
multi-state
conformations.
limitations
future
directions
discussed
as
well,
an
emphasis
on
potential
integration
experimental
techniques
further
refine
predictions.
Lastly,
work
underscores
transformative
contribution
computational
biology,
providing
insights
into
molecular
interactions
revolutionizing
accelerated
design
genomic
research.