bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 17, 2024
Abstract
G-Protein
Coupled
Receptors
(GPCRs)
are
membrane
proteins
implicated
in
numerous
diseases
that
have
been
studied
for
decades.
However,
despite
their
significance,
many
GPCRs
remain
poorly
characterized
and
untargeted
by
drugs.
Chimeric
emerged
as
valuable
tools
elucidating
GPCR
function
facilitating
the
identification
of
signaling
pathways,
resolving
structures,
discovering
novel
ligands
understood
GPCRs.
Such
chimeric
obtained
merging
a
well-characterized
less-well-characterized
at
intracellular
loops,
leveraging
knowledge
transfer
from
GPCR.
170
engineered
to
date,
design
process
remains
largely
trial-and-error
lacks
standardized
approach.
To
address
this
gap,
we
introduce
GPCRchimeraDB
(
https://www.bio2byte.be/gpcrchimeradb/
),
first
comprehensive
database
dedicated
It
catalogs
receptors,
identified
through
extensive
literature
review,
includes
1,758
natural
GPCRs,
enabling
connections
between
chimeras
parent
receptors
while
exploration
combinations.
Both
entries
extensively
described
sequence,
structural,
biophysical
level
range
visualization
tools,
with
annotations
resources
like
UniProt
GPCRdb
predictions
AlphaFold,
ESMFold
b2btools.
Additionally,
offers
sequence
aligner
feature
comparator
investigate
differences
well
guidelines
support
chimeras.
is
therefore
resource
facilitate
optimize
new
chimeras,
so
helping
gain
insights
into
contributing
advances
therapeutic
development.
Graphical
Life,
Journal Year:
2024,
Volume and Issue:
14(5), P. 548 - 548
Published: April 25, 2024
Olfactory
receptors
(ORs)
represent
one
of
the
largest
yet
least
investigated
families
G
protein-coupled
in
mammals.
While
initially
believed
to
be
functionally
restricted
detection
and
integration
odors
at
olfactory
epithelium,
accumulating
evidence
points
a
critical
role
for
ectopically
expressed
ORs
regulation
cellular
homeostasis
extranasal
tissues.
This
review
aims
summarize
current
state
knowledge
on
expression
physiological
functions
ectopic
cardiovascular
system,
kidneys,
primary
metabolic
organs
emphasizes
how
altered
OR
signaling
those
tissues
may
impact
cardiovascular-kidney-metabolic
health.
Protein Science,
Journal Year:
2025,
Volume and Issue:
34(5)
Published: April 18, 2025
Abstract
G
protein‐coupled
receptors
(GPCRs)
constitute
the
largest
transmembrane
protein
superfamily,
with
over
800
representatives
in
human
genome.
Recognized
as
pivotal
targets
pharmacological
research
and
drug
discovery,
these
play
a
crucial
role
advancing
therapeutics.
Understanding
molecular
mechanisms
of
receptor–ligand
interactions
is
imperative
for
discovery
applications.
However,
experimental
procedures
measuring
ligand
binding
are
complicated
by
various
factors,
including
nature
high
cost
associated
specialized
instruments
consumables.
Here
we
introduce
an
application
thermal
shift
assay
(TSA)
to
affinities
GPCRs.
TSA
cost‐effective
user‐friendly
method
that
detects
changes
stability
induced
alterations
environmental
conditions.
Employing
A
2A
adenosine
receptor
representative
GPCR,
determined
constants
four
orthosteric
ligands
allosteric
sodium
using
three
mathematical
models
data
approximation
analysis.
Models
were
additionally
validated
two
antagonists
cysteinyl
leukotriene
GPCR
(CysLT
1
R),
used
antiasthmatic
drugs.
Our
results
suggest
approach
demonstrates
degree
reproducibility
agreement
existing
literature
data,
thereby
affirming
its
suitability
investigating
types
ligands.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: April 9, 2024
Abstract
Background
and
Purpose
The
functional
G
protein-coupled
receptor
(GPCR)
signalling
unit
consists
of
an
agonist
acting
on
a
that
is
coupled
to
protein
transduces
the
signals
effectors
within
complex
cellular
environment.
While
much
attention
given
GPCR-agonist
or
GPCR-transducer
relationships,
contribution
environment
remains
significantly
unexplored.
Experimental
Approach
Here,
we
juxtaposed
responses
triggered
by
activation
two
GPCR
pattern
recognition
receptors,
Formyl
peptide
1
2,
in
recombinant
cell
system
against
their
dynamics
native
neutrophilic
Key
results
We
observed
leads
context-dependent
substantial
differences
texture.
impact
de
novo
cAMP
formation
varied
depending
type,
MAPK
was
similar
both
systems.
This
physiological
bias
conserved
across
species.
Expression
analysis
unveiled
absence
Gαi-sensitive
adenylyl
cyclases
ADCY5
ADCY6
neutrophils,
implying
synthesis
cannot
be
inhibited
Gαi-coupled
receptors.
behaviour
LTB4
high-affinity
BLT1
neutrophils
corroborated
our
findings.
Conclusion
Implications
Our
data
underscore
profound
specific
signalling,
causing
thereby
affecting
drug
efficacy
therapeutic
targeting.
Theoretical and Natural Science,
Journal Year:
2023,
Volume and Issue:
27(1), P. 251 - 256
Published: Dec. 19, 2023
As
a
class
of
proteins
that
play
crucial
roles
in
physiological
and
pathological
processes
within
the
human
body,
G
protein-coupled
receptors
(GPCRs)
have
emerged
as
prominent
targets
for
drug
development.
However,
there
is
still
ample
room
improvement
replacement
currently
developed
drugs
due
to
their
inherent
toxicity
associated
side
effects.
In
recent
years,
attention
has
shifted
towards
antibody-based
therapeutics
targeting
GPCRs,
owing
exceptional
specificity
low
plasma
clearance
rate.
This
review
provides
an
overview
fundamental
preparation
process
existing
challenges
encountered
developing
GPCR
antibody
drugs,
along
with
introduction
several
strategies
employed
formulation.
