Quarterly Reviews of Biophysics,
Год журнала:
2021,
Номер
54
Опубликована: Янв. 1, 2021
Over
the
past
decade,
structural
biology
of
membrane
proteins
(MPs)
has
taken
a
new
turn
thanks
to
epoch-making
technical
progress
in
single-particle
electron
cryo-microscopy
(cryo-EM)
as
well
improvements
sample
preparation.
The
present
analysis
provides
an
overview
extent
and
modes
usage
various
types
surfactants
for
cryo-EM
studies.
Digitonin,
dodecylmaltoside,
protein-based
nanodiscs,
lauryl
maltoside-neopentyl
glycol,
glyco-diosgenin,
amphipols
(APols)
are
most
popular
at
vitrification
step.
Surfactant
exchange
is
frequently
used
between
MP
purification
grid
preparation,
requiring
extensive
optimization
each
time
study
undertaken.
variety
both
experimental
approaches
over
few
years
bears
witness
need
continue
developing
innovative
optimizing
conditions
possibilities
offered
by
novel
APols
EM
applications
discussed.
Tetrameric
immune
receptors
Nucleotide-binding/leucine-rich
repeat
(NLR)
detect
pathogen
effectors
and
trigger
a
plant's
response.
Two
groups
have
now
defined
the
structures
of
two
NLRs
that
carry
Toll-like
interleukin-1
receptor
(TIR)
domains
(TIR-NLRs)
(see
Perspective
by
Tian
Li).
Ma
et
al.
studied
Arabidopsis
thaliana
TIR-NLR
RPP1
(recognition
Peronospora
parasitica
1)
its
response
to
from
an
oomycete
pathogen.
Martin
Nicotiana
benthamiana
ROQ1
XopQ
Xanthomonas
effector.
Both
found
these
TIR-NLRs
formed
tetramers
that,
when
activated
binding
effector,
exposed
active
site
nicotinamide
adenine
dinucleoside
(NAD)
hydrolase.
Thus,
recognition
effector
initiates
NAD
hydrolysis
begins
Science
,
this
issue
p.
eabe3069
eabd9993
;
see
also
1163
Drug Resistance Updates,
Год журнала:
2022,
Номер
66, С. 100905 - 100905
Опубликована: Ноя. 30, 2022
Multidrug
resistance
(MDR)
is
the
phenomenon
in
which
cancer
cells
simultaneously
develop
to
a
broad
spectrum
of
structurally
and
mechanistically
unrelated
drugs.
MDR
severely
hinders
effective
treatment
major
cause
chemotherapy
failure.
ATP-binding
cassette
(ABC)
transporters
are
extensively
expressed
various
body
tissues,
actively
transport
endogenous
exogenous
substrates
through
biological
membranes.
Overexpression
ABC
frequently
observed
cells,
promotes
efflux
chemotherapeutic
drugs
reduces
their
intracellular
accumulation.
Increasing
evidence
suggests
that
regulate
tumor
immune
microenvironment
(TIME)
by
transporting
cytokines,
thus
controlling
anti-tumor
immunity
sensitivity
anticancer
On
other
hand,
expression
regulated
cytokines
signaling
molecules.
Targeted
inhibition
transporter
or
function
can
enhance
efficacy
checkpoint
inhibitors
promoting
microenvironment.
This
review
provides
an
update
on
recent
research
progress
this
field.
Journal of Evidence-Based Medicine,
Год журнала:
2021,
Номер
14(3), С. 232 - 256
Опубликована: Авг. 13, 2021
Abstract
The
ATP‐binding
cassette
(ABC)
transporter
superfamily
is
one
of
the
largest
membrane
protein
families
existing
in
wide
spectrum
organisms
from
prokaryotes
to
human.
ABC
transporters
are
also
known
as
efflux
pumps
because
they
mediate
cross‐membrane
transportation
various
endo‐
and
xenobiotic
molecules
energized
by
ATP
hydrolysis.
Therefore,
have
been
considered
closely
multidrug
resistance
(MDR)
cancer,
where
structurally
distinct
chemotherapeutic
drugs
causes
reduced
itherapeutic
efficacy.
Besides,
play
other
critical
biological
roles
cancer
such
signal
transduction.
During
past
decades,
extensive
efforts
made
understanding
structure‐function
relationship,
profile
transporters,
well
possibility
overcome
MDR
via
targeting
these
transporters.
In
this
review,
we
discuss
most
recent
knowledge
regarding
drug
order
provide
insights
for
development
more
effective
therapies.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Июль 19, 2021
ABCG2
is
a
multidrug
transporter
that
affects
drug
pharmacokinetics
and
contributes
to
resistance
of
cancer
cells.
In
previously
reported
structures,
the
reaction
cycle
was
halted
by
absence
substrates
or
ATP,
mutation
catalytic
residues,
presence
small-molecule
inhibitors
inhibitory
antibodies.
Here
we
present
cryo-EM
structures
under
turnover
conditions
containing
either
endogenous
substrate
estrone-3-sulfate
exogenous
topotecan.
We
find
two
distinct
conformational
states
in
which
both
transport
ATP
are
bound.
Whereas
state
turnover-1
features
more
widely
separated
NBDs
an
accessible
cavity
between
TMDs,
turnover-2
semi-closed
almost
fully
occluded
cavity.
Substrate
size
appears
control
mainly
populated.
The
changes
reveal
how
binding
linked
closing
cytoplasmic
side
TMDs.
transition
from
likely
bottleneck
rate-limiting
step
cycle,
where
discrimination
occurs.
Proceedings of the National Academy of Sciences,
Год журнала:
2021,
Номер
118(48)
Опубликована: Ноя. 23, 2021
Significance
ATP-sensitive
potassium
channel
(K
ATP
)
modulates
membrane
excitability
according
to
the
intracellular
metabolic
state:
a
high
ATP/ADP
ratio
increases
by
closing
K
+
pore,
while
low
reduces
opening
it.
Such
intricate
regulation
is
achieved
allowing
and
ADP
act
upon
two
different
subunits
in
that
exert
opposing
effects
on
channel’s
gate.
Previous
structural
studies
have
focused
conformations
of
with
closed
pore.
This
paper
presents
structure
an
open
pore
points
specific
mechanism
allosteric
regulation.
Journal of Biological Chemistry,
Год журнала:
2021,
Номер
296, С. 100557 - 100557
Опубликована: Янв. 1, 2021
Biological
membranes
define
the
boundaries
of
cells
and
compartmentalize
chemical
physical
processes
required
for
life.
Many
biological
are
carried
out
by
proteins
embedded
in
or
associated
with
such
membranes.
Determination
membrane
protein
(MP)
structures
at
atomic
near-atomic
resolution
plays
a
vital
role
elucidating
their
structural
functional
impact
biology.
This
endeavor
has
determined
1198
unique
MP
as
early
2021.
The
value
these
is
expanded
greatly
deposition
three-dimensional
(3D)
coordinates
into
Protein
Data
Bank
(PDB)
after
first
structure
was
elucidated
1985.
Since
then,
free
access
to
facilitates
broader
deeper
understanding
MPs,
which
provides
crucial
new
insights
functions.
Here
we
highlight
biology
representative
MPs
landmarks
evolution
technologies,
key
developments
influenced
PDB
magnifying
impact.
Molecules,
Год журнала:
2023,
Номер
28(2), С. 495 - 495
Опубликована: Янв. 4, 2023
The
discovery
of
the
first
ATP-binding
cassette
(ABC)
transporter,
whose
overexpression
in
cancer
cells
is
responsible
for
exporting
anticancer
drugs
out
tumor
cells,
initiated
enormous
efforts
to
overcome
cell
multidrug
resistance
(MDR)
by
inhibition
ABC-transporter.
Because
its
many
physiological
functions,
diverse
studies
have
been
conducted
on
mechanism,
function
and
regulation
this
important
group
transmembrane
transport
proteins.
In
review,
we
will
focus
structural
aspects
transporter
superfamily.
Since
resolution
revolution
electron
microscope,
experimentally
solved
structures
increased
rapidly.
A
summary
available
an
overview
recent
structure-based
are
provided.
More
specifically,
artificial
intelligence
(AI)-based
predictions
from
AlphaFold-2
be
discussed.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Фев. 5, 2024
Bilirubin
is
mainly
generated
from
the
breakdown
of
heme
when
red
blood
cells
reach
end
their
lifespan.
Accumulation
bilirubin
in
human
body
usually
leads
to
various
disorders,
including
jaundice
and
liver
disease.
conjugated
hepatocytes
excreted
bile
duct
via
ATP-binding
cassette
transporter
ABCC2,
dysfunction
which
would
lead
Dubin-Johnson
syndrome.
Here
we
determine
structures
ABCC2
apo,
substrate-bound
ATP/ADP-bound
forms
using
cryo-electron
microscopy,
exhibiting
a
full
with
regulatory
(R)
domain
inserted
between
two
half
modules.
Combined
substrate-stimulated
ATPase
transport
activity
assays,
structural
analysis
enables
us
figure
out
cycle
R
adopting
conformations.
At
rest
state,
binding
translocation
cavity
functions
as
an
affinity
filter
that
allows
substrates
high
be
transported
priority.
Upon
substrate
binding,
expelled
docks
lateral
transmembrane
following
ATP
hydrolysis.
Our
findings
provide
insights
into
mechanism
ABC
transporters
finely
tuned
by
domain.