The Journal of Cell Biology,
Год журнала:
2024,
Номер
223(5)
Опубликована: Март 12, 2024
Mitochondria
transport
is
crucial
for
axonal
mitochondria
distribution
and
mediated
by
kinesin-1-based
anterograde
dynein-based
retrograde
motor
complexes.
While
Miro
Milton/TRAK
were
identified
as
key
adaptors
between
kinesin-1,
recent
studies
suggest
the
presence
of
additional
mechanisms.
In
C.
elegans,
ric-7
only
single
gene
described
so
far,
other
than
that
absolutely
required
localization.
Using
CRISPR
engineering
in
we
find
important
but
not
essential
traffic,
whereas
it
traffic.
Both
endogenous
RIC-7
kinesin-1
act
at
leading
end
to
anterogradely.
binding
requires
its
N-terminal
domain
partially
relies
on
MIRO-1,
accumulation
depends
disordered
region,
metaxin2.
We
conclude
complexes
containing
polarize
edge
are
elegans.
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,
Год журнала:
2024,
Номер
187(5), С. 1145 - 1159.e21
Опубликована: Фев. 1, 2024
Chloroplast
genes
encoding
photosynthesis-associated
proteins
are
predominantly
transcribed
by
the
plastid-encoded
RNA
polymerase
(PEP).
PEP
is
a
multi-subunit
complex
composed
of
subunits
similar
to
bacterial
polymerases
(RNAPs)
stably
bound
set
nuclear-encoded
PEP-associated
(PAPs).
PAPs
essential
activity
and
chloroplast
biogenesis,
but
their
roles
poorly
defined.
Here,
we
present
cryoelectron
microscopy
(cryo-EM)
structures
native
21-subunit
transcription
elongation
from
white
mustard
(Sinapis
alba).
We
identify
that
encase
core
polymerase,
forming
extensive
interactions
likely
promote
assembly
stability.
During
elongation,
interact
with
DNA
downstream
bubble
nascent
mRNA.
The
models
reveal
details
superoxide
dismutase,
lysine
methyltransferase,
thioredoxin,
amino
acid
ligase
enzymes
PEP.
Collectively,
these
data
provide
foundation
for
mechanistic
understanding
its
role
in
plant
growth
adaptation.
Structural Dynamics,
Год журнала:
2024,
Номер
11(3)
Опубликована: Май 1, 2024
Studying
protein
dynamics
and
conformational
heterogeneity
is
crucial
for
understanding
biomolecular
systems
treating
disease.
Despite
the
deposition
of
over
215
000
macromolecular
structures
in
Protein
Data
Bank
advent
AI-based
structure
prediction
tools
such
as
AlphaFold2,
RoseTTAFold,
ESMFold,
static
representations
are
typically
produced,
which
fail
to
fully
capture
motion.
Here,
we
discuss
importance
integrating
experimental
with
computational
clustering
explore
landscapes
that
manifest
function.
We
describe
method
developed
by
Europe
-
Knowledge
Base
identify
distinct
states,
demonstrate
resource's
primary
use
cases,
through
examples,
need
further
efforts
annotate
conformations
functional
information.
Such
initiatives
will
be
unlocking
potential
data,
expediting
drug
discovery
research,
deepening
our
mechanisms.
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(19)
Опубликована: Апрель 30, 2024
Targeting
proteins
to
specific
subcellular
destinations
is
essential
in
prokaryotes,
eukaryotes,
and
the
viruses
that
infect
them.
Chimalliviridae
phages
encapsulate
their
genomes
a
nucleus-like
replication
compartment
composed
of
protein
chimallin
(ChmA)
excludes
ribosomes
decouples
transcription
from
translation.
These
selectively
partition
between
phage
nucleus
bacterial
cytoplasm.
Currently,
genes
signals
govern
selective
import
into
are
unknown.
Here,
we
identify
two
components
this
pathway:
species-specific
surface-exposed
region
intranuclear
required
for
nuclear
entry
conserved
protein,
PicA
(Protein
importer
chimalliviruses
A),
facilitates
cargo
trafficking
across
shell.
We
also
defective
targeted
on
periphery
but
fails
enter
nucleus,
providing
insight
mechanism
trafficking.
Using
CRISPRi-ART
expression
knockdown
PicA,
show
early
chimallivirus
cycle.
Together,
our
results
allow
us
propose
multistep
model
Protein
Import
Chimallivirus
pathway,
where
by
amino
acids
surface
then
licensed
entry.
The
divergence
selectivity
pathway
closely
related
implicates
its
role
as
key
player
evolutionary
arms
race
competing
hosts.
npj Antimicrobials and Resistance,
Год журнала:
2025,
Номер
3(1)
Опубликована: Янв. 25, 2025
Since
its
discovery
nearly
60
years
ago,
TolC
has
been
associated
with
various
cellular
functions
in
Escherichia
coli,
including
the
efflux
of
environmental
stressors
and
virulence
factors.
It
also
acts
as
a
receptor
for
specific
bacteriophages
colicin
E1
toxin.
This
review
highlights
key
discoveries
over
past
six
decades
emphasizes
remaining
gaps
understanding
how
contributes
to
physiological
E.
coli.
Nucleic Acids Research,
Год журнала:
2023,
Номер
51(22), С. 12414 - 12427
Опубликована: Ноя. 16, 2023
RNA-guided
endonucleases
form
the
crux
of
diverse
biological
processes
and
technologies,
including
adaptive
immunity,
transposition,
genome
editing.
Some
these
enzymes
are
components
insertion
sequences
(IS)
in
IS200/IS605
IS607
transposon
families.
Both
IS
families
encode
a
TnpA
transposase
TnpB
nuclease,
an
enzyme
ancestral
to
CRISPR-Cas12s.
In
eukaryotes,
homologs
occur
as
two
distinct
types,
Fanzor1s
Fanzor2s.
We
analyzed
evolutionary
relationships
between
prokaryotic
TnpBs
eukaryotic
Fanzors,
which
revealed
that
both
Fanzor2s
stem
from
single
lineage
with
unusual
active
site
arrangement.
The
widespread
nature
Fanzors
implies
properties
this
particular
were
particularly
suited
adaptation
eukaryotes.
Biochemical
analysis
common
strategies
employed
by
co-evolve
their
cognate
transposases.
Collectively,
our
results
provide
new
model
sequential
evolution
Fanzor2s,
details
how
genes
origin
evolve
give
rise
protein