Role of N343 glycosylation on the SARS-CoV-2 S RBD structure and co-receptor binding across variants of concern
eLife,
Год журнала:
2024,
Номер
13
Опубликована: Март 27, 2024
Glycosylation
of
the
SARS-CoV-2
spike
(S)
protein
represents
a
key
target
for
viral
evolution
because
it
affects
both
evasion
and
fitness.
Successful
variations
in
glycan
shield
are
difficult
to
achieve
though,
as
glycosylation
is
also
critical
folding
structural
stability.
Within
this
framework,
identification
sites
that
structurally
dispensable
can
provide
insight
into
evolutionary
mechanisms
inform
immune
surveillance.
In
work,
we
show
through
over
45
μs
cumulative
sampling
from
conventional
enhanced
molecular
dynamics
(MD)
simulations,
how
structure
immunodominant
S
receptor
binding
domain
(RBD)
regulated
by
N
-glycosylation
at
N343
glycan’s
role
changes
WHu-1,
alpha
(B.1.1.7),
beta
(B.1.351),
delta
(B.1.617.2),
omicron
(BA.1
BA.2.86)
variants.
More
specifically,
find
amphipathic
nature
-glycan
instrumental
preserve
integrity
RBD
hydrophobic
core
loss
triggers
specific
consistent
conformational
change.
We
change
allosterically
regulates
conformation
motif
(RBM)
alpha,
RBDs,
but
not
variants,
due
mutations
reinforce
architecture.
support
these
findings,
monosialylated
ganglioside
co-receptors
highly
dependent
on
RBD,
affinity
significantly
across
VoCs.
Ultimately,
functional
work
reinforces
our
understanding
function
allows
us
identify
constraints
within
which
site
become
hotspot
shield.
Язык: Английский
Structural and Functional Glycosylation of the Abdala COVID-19 Vaccine
Glycobiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 12, 2025
Abstract
Abdala
is
a
COVID-19
vaccine
produced
in
Pichia
pastoris
and
based
on
the
receptor-binding
domain
(RBD)
of
SARS-CoV-2
spike.
currently
approved
for
use
multiple
countries
with
clinical
trials
confirming
its
safety
efficacy
preventing
severe
illness
death.
Although
P.
used
as
an
expression
system
protein-based
vaccines,
yeast
glycosylation
remains
largely
uncharacterised
across
immunogens.
Here,
we
characterise
N-glycan
structures
their
site
attachment
show
how
yeast-specific
decreases
binding
to
ACE2
receptor
motif
(RBM)
targeting
antibody
compared
equivalent
mammalian-derived
RBD.
Reduced
attributed
changes
conformational
dynamics
resulting
from
N-glycosylation.
These
data
highlight
critical
importance
design
demonstrate
individual
glycans
can
influence
host
interactions
immune
recognition
via
protein
structural
dynamics.
Язык: Английский
Changes in the dynamic characteristics of G-protein can alter the immune-protection efficacy of rabies virus vaccine
Journal of Virology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 21, 2025
ABSTRACT
The
efficacy
of
the
G-protein
is
influenced
by
N-linked
glycosylation,
which
serves
as
sole
immunogen
rabies
virus
vaccine.
However,
achieving
satisfactory
immune-protection
remains
challenging,
owing
to
heterogeneous
glycosylation
G-proteins.
Within
molecular
dynamics,
examining
impact
N-glycan
heterogeneity
on
structural
characteristics
G-proteins
provides
insights
into
relationship
between
antigens
and
vaccines.
Glycosylation
regulated
host
cells.
In
cultured
in
Vero
cells
(VRV),
all
N-glycosylation
sites
underwent
modification.
contrast,
KMB17
(human
diploid
cell
vaccine
[HDCV])
was
only
modified
N-glycans
at
amino
acid
positions
247
319.
Furthermore,
treatment
VRV
with
de-glycosylation
significantly
improved
its
immune-protective
efficacy,
whereas
did
not
alter
HDCV.
To
support
structures
dynamics
were
analyzed
using
GROMACS.
Specifically,
hydrophobicity,
flexibility,
radius
gyration
trimer
altered
excessive
hydrogen
bonds
formed
three-branched
hybrid
glycan
aa
319
site.
These
changes
increase
instability
may
lead
a
decrease
protective
efficacy.
Ultimately,
we
determined
that
affects
effect
antigen
proteins
altering
their
dynamic
characteristics,
enhancing
our
understanding
correlation
IMPORTANCE
glycoprotein
dynamically
regulates
protein
folding,
stability,
antigenicity.
Therefore,
regulation
modification
key
improving
stability
How
type
affect
vaccines
unclear.
Our
research
indicates
there
are
differences
different
N-glycans.
Moreover,
site
radius,
increased
trimeric
through
demonstrations.
findings
update
current
glycans
antigenicity
develop
system
evaluate
glycoproteins
based
dynamics.
Язык: Английский
Structure and dynamics of the interaction of Delta and Omicron BA.1 SARS-CoV-2 variants with REGN10987 Fab reveal mechanism of antibody action
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Дек. 24, 2024
Study
of
mechanisms
by
which
antibodies
recognize
different
viral
strains
is
necessary
for
the
development
new
drugs
and
vaccines
to
treat
COVID-19
other
infections.
Here,
we
report
2.5
Å
cryo-EM
structure
SARS-CoV-2
Delta
trimeric
S-protein
in
complex
with
Fab
recombinant
analog
REGN10987
neutralizing
antibody.
adopts
"two
RBD-down
one
RBD-up"
conformation.
interacts
RBDs
both
conformations,
blocking
recognition
angiotensin
converting
enzyme-2.
Three-dimensional
variability
analysis
reveals
high
mobility
RBD/Fab
regions.
Interaction
Wuhan,
Delta,
Omicron
BA.1,
mutated
variants
analyzed
microscale
thermophoresis,
molecular
dynamics
simulations,
ΔG
calculations
umbrella
sampling
one-dimensional
potential
mean
force.
Variability
trajectories
results
a
large
scatter
calculated
values,
but
Boltzmann
weighting
provides
an
acceptable
correlation
experiment.
evasion
variant
found
be
due
additive
effect
N440K
G446S
mutations
located
at
binding
interface
small
Q498R
mutation.
Our
study
explains
influence
known-to-date
RBD
on
highlights
importance
data
beyond
static
complex.
Cryo-EM
Sprotein
REGN10987,
MD
simulations
variants,
explain
role
individual
evasion.
Язык: Английский