Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity.
Identifieur interne : 002F05 ( Main/Exploration ); précédent : 002F04; suivant : 002F06Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity.
Auteurs : Eneko Urizar [Belgique] ; Lucia Montanelli ; Tiffany Loy ; Marco Bonomi ; Stéphane Swillens ; Céline Gales ; Michel Bouvier ; Guillaume Smits ; Gilbert Vassart ; Sabine CostagliolaSource :
- The EMBO journal [ 0261-4189 ] ; 2005.
Descripteurs français
- KwdFr :
- AMP cyclique (biosynthèse), Animaux, Cartographie d'interactions entre protéines, Dimérisation, Equus caballus, Glande thyroide (métabolisme), Humains, Liaison aux protéines, Lignée cellulaire, Membrane cellulaire (métabolisme), Modèles moléculaires, Multimérisation de protéines, Protéines bactériennes (analyse), Protéines de fusion recombinantes (), Protéines de fusion recombinantes (métabolisme), Protéines luminescentes (analyse), Rein, Récepteur FSH (), Récepteur FSH (métabolisme), Récepteur LH (), Récepteur LH (métabolisme), Récepteur TSH (), Récepteur TSH (métabolisme), Régulation allostérique, Sites de fixation, Structure tertiaire des protéines, Sus scrofa, Transfection, Transfert d'énergie par résonance de fluorescence.
- MESH :
- analyse : Protéines bactériennes, Protéines luminescentes.
- biosynthèse : AMP cyclique.
- métabolisme : Glande thyroide, Membrane cellulaire, Protéines de fusion recombinantes, Récepteur FSH, Récepteur LH, Récepteur TSH.
- Animaux, Cartographie d'interactions entre protéines, Dimérisation, Equus caballus, Humains, Liaison aux protéines, Lignée cellulaire, Modèles moléculaires, Multimérisation de protéines, Protéines de fusion recombinantes, Rein, Récepteur FSH, Récepteur LH, Récepteur TSH, Régulation allostérique, Sites de fixation, Structure tertiaire des protéines, Sus scrofa, Transfection, Transfert d'énergie par résonance de fluorescence.
English descriptors
- KwdEn :
- Allosteric Regulation, Animals, Bacterial Proteins (analysis), Binding Sites, Cell Line, Cell Membrane (metabolism), Cyclic AMP (biosynthesis), Dimerization, Fluorescence Resonance Energy Transfer, Horses, Humans, Kidney, Luminescent Proteins (analysis), Models, Molecular, Protein Binding, Protein Interaction Mapping, Protein Multimerization, Protein Structure, Tertiary, Receptors, FSH (chemistry), Receptors, FSH (metabolism), Receptors, LH (chemistry), Receptors, LH (metabolism), Receptors, Thyrotropin (chemistry), Receptors, Thyrotropin (metabolism), Recombinant Fusion Proteins (chemistry), Recombinant Fusion Proteins (metabolism), Sus scrofa, Thyroid Gland (metabolism), Transfection.
- MESH :
- chemical , analysis : Bacterial Proteins, Luminescent Proteins.
- chemical , biosynthesis : Cyclic AMP.
- chemical , chemistry : Receptors, FSH, Receptors, LH, Receptors, Thyrotropin, Recombinant Fusion Proteins.
- metabolism : Cell Membrane, Receptors, FSH, Receptors, LH, Receptors, Thyrotropin, Recombinant Fusion Proteins, Thyroid Gland.
- Allosteric Regulation, Animals, Binding Sites, Cell Line, Dimerization, Fluorescence Resonance Energy Transfer, Horses, Humans, Kidney, Models, Molecular, Protein Binding, Protein Interaction Mapping, Protein Multimerization, Protein Structure, Tertiary, Sus scrofa, Transfection.
Abstract
The monomeric model of rhodopsin-like G protein-coupled receptors (GPCRs) has progressively yielded the floor to the concept of GPCRs being oligo(di)mers, but the functional correlates of dimerization remain unclear. In this report, dimers of glycoprotein hormone receptors were demonstrated in living cells, with a combination of biophysical (bioluminescence resonance energy transfer and homogenous time resolved fluorescence/fluorescence resonance energy transfer), functional and biochemical approaches. Thyrotropin (TSHr) and lutropin (LH/CGr) receptors form homo- and heterodimers, via interactions involving primarily their heptahelical domains. The large hormone-binding ectodomains were dispensable for dimerization but modulated protomer interaction. Dimerization was not affected by agonist binding. Observed functional complementation indicates that TSHr dimers may function as a single functional unit. Finally, heterologous binding-competition studies, performed with heterodimers between TSHr and LH/CG-TSHr chimeras, demonstrated the unsuspected existence of strong negative cooperativity of hormone binding. Tracer desorption experiments indicated an allosteric behavior in TSHr and, to a lesser extent, in LH/CGr and FSHr homodimers. This study is the first report of homodimerization associated with negative cooperativity in rhodopsin-like GPCRs. As such, it may warrant revisitation of allosterism in the whole GPCR family.
DOI: 10.1038/sj.emboj.7600686
PubMed: 15889138
Affiliations:
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Le document en format XML
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Lucia" uniqKey="Montanelli L" first="Lucia" last="Montanelli">Lucia Montanelli</name></author><author><name sortKey="Loy, Tiffany" sort="Loy, Tiffany" uniqKey="Loy T" first="Tiffany" last="Loy">Tiffany Loy</name></author><author><name sortKey="Bonomi, Marco" sort="Bonomi, Marco" uniqKey="Bonomi M" first="Marco" last="Bonomi">Marco Bonomi</name></author><author><name sortKey="Swillens, Stephane" sort="Swillens, Stephane" uniqKey="Swillens S" first="Stéphane" last="Swillens">Stéphane Swillens</name></author><author><name sortKey="Gales, Celine" sort="Gales, Celine" uniqKey="Gales C" first="Céline" last="Gales">Céline Gales</name></author><author><name sortKey="Bouvier, Michel" sort="Bouvier, Michel" uniqKey="Bouvier M" first="Michel" last="Bouvier">Michel Bouvier</name></author><author><name sortKey="Smits, Guillaume" sort="Smits, Guillaume" uniqKey="Smits G" first="Guillaume" last="Smits">Guillaume Smits</name></author><author><name sortKey="Vassart, Gilbert" sort="Vassart, Gilbert" 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Mapping</term><term>Protein Multimerization</term><term>Protein Structure, Tertiary</term><term>Receptors, FSH (chemistry)</term><term>Receptors, FSH (metabolism)</term><term>Receptors, LH (chemistry)</term><term>Receptors, LH (metabolism)</term><term>Receptors, Thyrotropin (chemistry)</term><term>Receptors, Thyrotropin (metabolism)</term><term>Recombinant Fusion Proteins (chemistry)</term><term>Recombinant Fusion Proteins (metabolism)</term><term>Sus scrofa</term><term>Thyroid Gland (metabolism)</term><term>Transfection</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>AMP cyclique (biosynthèse)</term><term>Animaux</term><term>Cartographie d'interactions entre protéines</term><term>Dimérisation</term><term>Equus caballus</term><term>Glande thyroide (métabolisme)</term><term>Humains</term><term>Liaison aux protéines</term><term>Lignée cellulaire</term><term>Membrane cellulaire (métabolisme)</term><term>Modèles moléculaires</term><term>Multimérisation de protéines</term><term>Protéines bactériennes (analyse)</term><term>Protéines de fusion recombinantes ()</term><term>Protéines de fusion recombinantes (métabolisme)</term><term>Protéines luminescentes (analyse)</term><term>Rein</term><term>Récepteur FSH ()</term><term>Récepteur FSH (métabolisme)</term><term>Récepteur LH ()</term><term>Récepteur LH (métabolisme)</term><term>Récepteur TSH ()</term><term>Récepteur TSH (métabolisme)</term><term>Régulation allostérique</term><term>Sites de fixation</term><term>Structure tertiaire des protéines</term><term>Sus scrofa</term><term>Transfection</term><term>Transfert d'énergie par résonance de fluorescence</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Bacterial Proteins</term><term>Luminescent Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cyclic AMP</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Receptors, FSH</term><term>Receptors, LH</term><term>Receptors, Thyrotropin</term><term>Recombinant Fusion Proteins</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Protéines bactériennes</term><term>Protéines luminescentes</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>AMP cyclique</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cell Membrane</term><term>Receptors, FSH</term><term>Receptors, LH</term><term>Receptors, Thyrotropin</term><term>Recombinant Fusion Proteins</term><term>Thyroid Gland</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glande thyroide</term><term>Membrane cellulaire</term><term>Protéines de fusion recombinantes</term><term>Récepteur FSH</term><term>Récepteur LH</term><term>Récepteur TSH</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Allosteric Regulation</term><term>Animals</term><term>Binding Sites</term><term>Cell Line</term><term>Dimerization</term><term>Fluorescence Resonance Energy Transfer</term><term>Horses</term><term>Humans</term><term>Kidney</term><term>Models, Molecular</term><term>Protein Binding</term><term>Protein Interaction Mapping</term><term>Protein Multimerization</term><term>Protein Structure, Tertiary</term><term>Sus scrofa</term><term>Transfection</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cartographie d'interactions entre protéines</term><term>Dimérisation</term><term>Equus caballus</term><term>Humains</term><term>Liaison aux protéines</term><term>Lignée cellulaire</term><term>Modèles moléculaires</term><term>Multimérisation de protéines</term><term>Protéines de fusion recombinantes</term><term>Rein</term><term>Récepteur FSH</term><term>Récepteur LH</term><term>Récepteur TSH</term><term>Régulation allostérique</term><term>Sites de fixation</term><term>Structure tertiaire des protéines</term><term>Sus scrofa</term><term>Transfection</term><term>Transfert d'énergie par résonance de fluorescence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The monomeric model of rhodopsin-like G protein-coupled receptors (GPCRs) has progressively yielded the floor to the concept of GPCRs being oligo(di)mers, but the functional correlates of dimerization remain unclear. In this report, dimers of glycoprotein hormone receptors were demonstrated in living cells, with a combination of biophysical (bioluminescence resonance energy transfer and homogenous time resolved fluorescence/fluorescence resonance energy transfer), functional and biochemical approaches. Thyrotropin (TSHr) and lutropin (LH/CGr) receptors form homo- and heterodimers, via interactions involving primarily their heptahelical domains. The large hormone-binding ectodomains were dispensable for dimerization but modulated protomer interaction. Dimerization was not affected by agonist binding. Observed functional complementation indicates that TSHr dimers may function as a single functional unit. Finally, heterologous binding-competition studies, performed with heterodimers between TSHr and LH/CG-TSHr chimeras, demonstrated the unsuspected existence of strong negative cooperativity of hormone binding. Tracer desorption experiments indicated an allosteric behavior in TSHr and, to a lesser extent, in LH/CGr and FSHr homodimers. This study is the first report of homodimerization associated with negative cooperativity in rhodopsin-like GPCRs. As such, it may warrant revisitation of allosterism in the whole GPCR family.</div></front></TEI><affiliations><list><country><li>Belgique</li></country><region><li>Région de Bruxelles-Capitale</li></region><settlement><li>Bruxelles</li></settlement><orgName><li>Université libre de Bruxelles</li></orgName></list><tree><noCountry><name sortKey="Bonomi, Marco" sort="Bonomi, Marco" uniqKey="Bonomi M" first="Marco" last="Bonomi">Marco Bonomi</name><name sortKey="Bouvier, Michel" sort="Bouvier, Michel" uniqKey="Bouvier M" first="Michel" last="Bouvier">Michel Bouvier</name><name sortKey="Costagliola, Sabine" sort="Costagliola, Sabine" uniqKey="Costagliola S" first="Sabine" last="Costagliola">Sabine Costagliola</name><name sortKey="Gales, Celine" sort="Gales, Celine" uniqKey="Gales C" first="Céline" last="Gales">Céline Gales</name><name sortKey="Loy, Tiffany" sort="Loy, Tiffany" uniqKey="Loy T" first="Tiffany" last="Loy">Tiffany Loy</name><name sortKey="Montanelli, Lucia" sort="Montanelli, Lucia" uniqKey="Montanelli L" first="Lucia" last="Montanelli">Lucia Montanelli</name><name sortKey="Smits, Guillaume" sort="Smits, Guillaume" uniqKey="Smits G" first="Guillaume" last="Smits">Guillaume Smits</name><name sortKey="Swillens, Stephane" sort="Swillens, Stephane" uniqKey="Swillens S" first="Stéphane" last="Swillens">Stéphane Swillens</name><name sortKey="Vassart, Gilbert" sort="Vassart, Gilbert" uniqKey="Vassart G" first="Gilbert" last="Vassart">Gilbert Vassart</name></noCountry><country name="Belgique"><region name="Région de Bruxelles-Capitale"><name sortKey="Urizar, Eneko" sort="Urizar, Eneko" uniqKey="Urizar E" first="Eneko" last="Urizar">Eneko Urizar</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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