Molecular basis of inverse agonism in a G protein-coupled receptor
J. Vilardaga, R. Steinmeyer, G. Harms, и M. Lohse. Nat Chem Biol, 1 (1):
25-8(июня 2005)Vilardaga, Jean-Pierre Steinmeyer, Ralf Harms, Greg S Lohse, Martin
J Research Support, Non-U.S. Gov't United States Nature chemical
biology Nat Chem Biol. 2005 Jun;1(1):25-8. Epub 2005 May 24..
Аннотация
G protein-coupled receptors (GPCRs) recognize a wide variety of extracellular
ligands to control diverse physiological processes. Compounds that
bind to such receptors can either stimulate, fully or partially (full
or partial agonists), or reduce (inverse agonists) the receptors'
basal activity and receptor-mediated signaling. Various studies have
shown that the activation of receptors through binding of agonists
proceeds by conformational changes as the receptor switches from
a resting to an active state leading to G protein signaling. Yet
the molecular basis for differences between agonists and inverse
agonists is unclear. These different classes of compounds are assumed
to switch the receptors' conformation in distinct ways. It is not
known, however, whether such switching occurs along a linear 'on-off'
scale or whether agonists and inverse agonists induce different switch
mechanisms. Using a fluorescence-based approach to study the alpha2A-adrenergic
receptor (alpha(2A)AR), we show that inverse agonists are differentiated
from agonists in that they trigger a very distinct mode of a receptor's
switch. This switch couples inverse agonist binding to the suppression
of activity in the receptor.
Vilardaga, Jean-Pierre Steinmeyer, Ralf Harms, Greg S Lohse, Martin
J Research Support, Non-U.S. Gov't United States Nature chemical
biology Nat Chem Biol. 2005 Jun;1(1):25-8. Epub 2005 May 24.
%0 Journal Article
%1 Vilardaga2005
%A Vilardaga, J. P.
%A Steinmeyer, R.
%A Harms, G. S.
%A Lohse, M. J.
%D 2005
%J Nat Chem Biol
%K Binding Cell Energy Fluorescence G-Protein-Coupled/*agonists Humans Ligands Line Protein Resonance Signal Transduction/*drug Transfer alpha-2/agonists effects Receptor Adrenergic
%N 1
%P 25-8
%T Molecular basis of inverse agonism in a G protein-coupled receptor
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16407989
%V 1
%X G protein-coupled receptors (GPCRs) recognize a wide variety of extracellular
ligands to control diverse physiological processes. Compounds that
bind to such receptors can either stimulate, fully or partially (full
or partial agonists), or reduce (inverse agonists) the receptors'
basal activity and receptor-mediated signaling. Various studies have
shown that the activation of receptors through binding of agonists
proceeds by conformational changes as the receptor switches from
a resting to an active state leading to G protein signaling. Yet
the molecular basis for differences between agonists and inverse
agonists is unclear. These different classes of compounds are assumed
to switch the receptors' conformation in distinct ways. It is not
known, however, whether such switching occurs along a linear 'on-off'
scale or whether agonists and inverse agonists induce different switch
mechanisms. Using a fluorescence-based approach to study the alpha2A-adrenergic
receptor (alpha(2A)AR), we show that inverse agonists are differentiated
from agonists in that they trigger a very distinct mode of a receptor's
switch. This switch couples inverse agonist binding to the suppression
of activity in the receptor.
@article{Vilardaga2005,
abstract = {G protein-coupled receptors (GPCRs) recognize a wide variety of extracellular
ligands to control diverse physiological processes. Compounds that
bind to such receptors can either stimulate, fully or partially (full
or partial agonists), or reduce (inverse agonists) the receptors'
basal activity and receptor-mediated signaling. Various studies have
shown that the activation of receptors through binding of agonists
proceeds by conformational changes as the receptor switches from
a resting to an active state leading to G protein signaling. Yet
the molecular basis for differences between agonists and inverse
agonists is unclear. These different classes of compounds are assumed
to switch the receptors' conformation in distinct ways. It is not
known, however, whether such switching occurs along a linear 'on-off'
scale or whether agonists and inverse agonists induce different switch
mechanisms. Using a fluorescence-based approach to study the alpha2A-adrenergic
receptor (alpha(2A)AR), we show that inverse agonists are differentiated
from agonists in that they trigger a very distinct mode of a receptor's
switch. This switch couples inverse agonist binding to the suppression
of activity in the receptor.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Vilardaga, J. P. and Steinmeyer, R. and Harms, G. S. and Lohse, M. J.},
biburl = {https://www.bibsonomy.org/bibtex/2014278d99b5f21fe6baadec708cb110b/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {26c614e4e650d07d94815f6254684b80},
intrahash = {014278d99b5f21fe6baadec708cb110b},
issn = {1552-4450 (Print)},
journal = {Nat Chem Biol},
keywords = {Binding Cell Energy Fluorescence G-Protein-Coupled/*agonists Humans Ligands Line Protein Resonance Signal Transduction/*drug Transfer alpha-2/agonists effects Receptor Adrenergic},
month = Jun,
note = {Vilardaga, Jean-Pierre Steinmeyer, Ralf Harms, Greg S Lohse, Martin
J Research Support, Non-U.S. Gov't United States Nature chemical
biology Nat Chem Biol. 2005 Jun;1(1):25-8. Epub 2005 May 24.},
number = 1,
pages = {25-8},
shorttitle = {Molecular basis of inverse agonism in a G protein-coupled receptor},
timestamp = {2010-12-14T18:22:43.000+0100},
title = {Molecular basis of inverse agonism in a G protein-coupled receptor},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16407989},
volume = 1,
year = 2005
}