Solution conformation of the antibody-bound tyrosine phosphorylation site of the nicotinic acetylcholine receptor beta-subunit in its phosphorylated and nonphosphorylated states.
Identifieur interne : 001638 ( Main/Exploration ); précédent : 001637; suivant : 001639Solution conformation of the antibody-bound tyrosine phosphorylation site of the nicotinic acetylcholine receptor beta-subunit in its phosphorylated and nonphosphorylated states.
Auteurs : Angélique Phan-Chan-Du [France] ; Christine Hemmerlin ; Dimitrios Krikorian ; Maria Sakarellos-Daitsiotis ; Vassilios Tsikaris ; Constantinos Sakarellos ; Martha Marinou ; Aurélien Thureau ; Manh Thong Cung ; Socrates J. TzartosSource :
- Biochemistry [ 0006-2960 ] ; 2003.
Descripteurs français
- KwdFr :
- Animaux, Anticorps monoclonaux (), Anticorps monoclonaux (métabolisme), Canaux ioniques (antagonistes et inhibiteurs), Conformation des protéines, Dosage radioimmunologique, Fixation compétitive, Humains, Modèles moléculaires, Peptides (), Peptides (génétique), Peptides (pharmacologie), Phosphorylation, Relation structure-activité, Récepteurs nicotiniques (), Récepteurs nicotiniques (génétique), Récepteurs nicotiniques (métabolisme), Résonance magnétique nucléaire biomoléculaire, Sites de fixation, Solutions, Sous-unités de protéines, Séquence d'acides aminés, Test ELISA, Torpedo (métabolisme), Tyrosine (métabolisme).
- MESH :
- antagonistes et inhibiteurs : Canaux ioniques.
- génétique : Peptides, Récepteurs nicotiniques.
- métabolisme : Anticorps monoclonaux, Récepteurs nicotiniques, Torpedo, Tyrosine.
- pharmacologie : Peptides.
- Animaux, Anticorps monoclonaux, Conformation des protéines, Dosage radioimmunologique, Fixation compétitive, Humains, Modèles moléculaires, Peptides, Phosphorylation, Relation structure-activité, Récepteurs nicotiniques, Résonance magnétique nucléaire biomoléculaire, Sites de fixation, Solutions, Sous-unités de protéines, Séquence d'acides aminés, Test ELISA.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Monoclonal (chemistry), Antibodies, Monoclonal (metabolism), Binding Sites, Binding, Competitive, Enzyme-Linked Immunosorbent Assay, Humans, Ion Channels (antagonists & inhibitors), Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Peptides (chemistry), Peptides (genetics), Peptides (pharmacology), Phosphorylation, Protein Conformation, Protein Subunits, Radioimmunoassay, Receptors, Nicotinic (chemistry), Receptors, Nicotinic (genetics), Receptors, Nicotinic (metabolism), Solutions, Structure-Activity Relationship, Torpedo (metabolism), Tyrosine (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Ion Channels.
- chemical , chemistry : Antibodies, Monoclonal, Peptides, Receptors, Nicotinic.
- chemical , genetics : Peptides, Receptors, Nicotinic.
- chemical , metabolism : Antibodies, Monoclonal, Receptors, Nicotinic, Tyrosine.
- chemical , pharmacology : Peptides.
- metabolism : Torpedo.
- Amino Acid Sequence, Animals, Binding Sites, Binding, Competitive, Enzyme-Linked Immunosorbent Assay, Humans, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Phosphorylation, Protein Conformation, Protein Subunits, Radioimmunoassay, Solutions, Structure-Activity Relationship.
Abstract
Phosphorylation of the acetylcholine receptor (AChR) seems to be responsible for triggering several effects including its desensitization and aggregation at the postsynaptic membrane and probably initiates a signal transduction pathway at the postsynaptic membrane. To study the structural and functional role of the tyrosine phosphorylation site of the AChR beta-subunit and contribute to the in-depth understanding of the structural basis of the ion channel function, we synthesized four peptides containing the phosphorylated and nonphosphorylated sequences (380-391) of the human and Torpedo AChR beta-subunits and studied their interaction with a monoclonal antibody (mAb 148) that is known to bind to this region and that is capable of blocking ion channel function. All four peptides were efficient inhibitors of mAb 148 binding to AChR, although the nonphosphorylated human peptide was considerably less effective than the three others. We then investigated the conformation acquired by all four peptides in their antibody-bound state, which possibly illustrates the local conformation of the corresponding sites on the intact AChR molecule. The phosphorylated human and Torpedo peptides adopted a distorted 3(10) helix conformation. The nonphosphorylated Torpedo peptide, which is also an efficient inhibitor, was also folded. In contrast, the nonphosphorylated human peptide (a less efficient inhibitor) presented an extended structure. It is concluded that the phosphorylation of the AChR at its beta-subunit Tyr site leads to a significant change in its conformation, which may affect several functions of the AChR.
DOI: 10.1021/bi030034u
PubMed: 12809492
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000203
- to stream PubMed, to step Curation: 000203
- to stream PubMed, to step Checkpoint: 000203
- to stream Ncbi, to step Merge: 000033
- to stream Ncbi, to step Curation: 000033
- to stream Ncbi, to step Checkpoint: 000033
- to stream Main, to step Merge: 001886
- to stream Main, to step Curation: 001638
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Solution conformation of the antibody-bound tyrosine phosphorylation site of the nicotinic acetylcholine receptor beta-subunit in its phosphorylated and nonphosphorylated states.</title><author><name sortKey="Phan Chan Du, Angelique" sort="Phan Chan Du, Angelique" uniqKey="Phan Chan Du A" first="Angélique" last="Phan-Chan-Du">Angélique Phan-Chan-Du</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Chimie-Physique Macromoléculaire, UMR 7568 CNRS-INPL, Groupe ENSIC, 1 Rue Grandville, B.P. 451, 54001 Nancy Cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Chimie-Physique Macromoléculaire, UMR 7568 CNRS-INPL, Groupe ENSIC, 1 Rue Grandville, B.P. 451, 54001 Nancy Cedex</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Hemmerlin, Christine" sort="Hemmerlin, Christine" uniqKey="Hemmerlin C" first="Christine" last="Hemmerlin">Christine Hemmerlin</name></author><author><name sortKey="Krikorian, Dimitrios" sort="Krikorian, Dimitrios" uniqKey="Krikorian D" first="Dimitrios" last="Krikorian">Dimitrios Krikorian</name></author><author><name sortKey="Sakarellos Daitsiotis, Maria" sort="Sakarellos Daitsiotis, Maria" uniqKey="Sakarellos Daitsiotis M" first="Maria" last="Sakarellos-Daitsiotis">Maria Sakarellos-Daitsiotis</name></author><author><name sortKey="Tsikaris, Vassilios" sort="Tsikaris, Vassilios" uniqKey="Tsikaris V" first="Vassilios" last="Tsikaris">Vassilios Tsikaris</name></author><author><name sortKey="Sakarellos, Constantinos" sort="Sakarellos, Constantinos" uniqKey="Sakarellos C" first="Constantinos" last="Sakarellos">Constantinos Sakarellos</name></author><author><name sortKey="Marinou, Martha" sort="Marinou, Martha" uniqKey="Marinou M" first="Martha" last="Marinou">Martha Marinou</name></author><author><name sortKey="Thureau, Aurelien" sort="Thureau, Aurelien" uniqKey="Thureau A" first="Aurélien" last="Thureau">Aurélien Thureau</name></author><author><name sortKey="Cung, Manh Thong" sort="Cung, Manh Thong" uniqKey="Cung M" first="Manh Thong" last="Cung">Manh Thong Cung</name></author><author><name sortKey="Tzartos, Socrates J" sort="Tzartos, Socrates J" uniqKey="Tzartos S" first="Socrates J" last="Tzartos">Socrates J. Tzartos</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2003">2003</date><idno type="RBID">pubmed:12809492</idno><idno type="pmid">12809492</idno><idno type="doi">10.1021/bi030034u</idno><idno type="wicri:Area/PubMed/Corpus">000203</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000203</idno><idno type="wicri:Area/PubMed/Curation">000203</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000203</idno><idno type="wicri:Area/PubMed/Checkpoint">000203</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000203</idno><idno type="wicri:Area/Ncbi/Merge">000033</idno><idno type="wicri:Area/Ncbi/Curation">000033</idno><idno type="wicri:Area/Ncbi/Checkpoint">000033</idno><idno type="wicri:doubleKey">0006-2960:2003:Phan Chan Du A:solution:conformation:of</idno><idno type="wicri:Area/Main/Merge">001886</idno><idno type="wicri:Area/Main/Curation">001638</idno><idno type="wicri:Area/Main/Exploration">001638</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Solution conformation of the antibody-bound tyrosine phosphorylation site of the nicotinic acetylcholine receptor beta-subunit in its phosphorylated and nonphosphorylated states.</title><author><name sortKey="Phan Chan Du, Angelique" sort="Phan Chan Du, Angelique" uniqKey="Phan Chan Du A" first="Angélique" last="Phan-Chan-Du">Angélique Phan-Chan-Du</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Chimie-Physique Macromoléculaire, UMR 7568 CNRS-INPL, Groupe ENSIC, 1 Rue Grandville, B.P. 451, 54001 Nancy Cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Chimie-Physique Macromoléculaire, UMR 7568 CNRS-INPL, Groupe ENSIC, 1 Rue Grandville, B.P. 451, 54001 Nancy Cedex</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Hemmerlin, Christine" sort="Hemmerlin, Christine" uniqKey="Hemmerlin C" first="Christine" last="Hemmerlin">Christine Hemmerlin</name></author><author><name sortKey="Krikorian, Dimitrios" sort="Krikorian, Dimitrios" uniqKey="Krikorian D" first="Dimitrios" last="Krikorian">Dimitrios Krikorian</name></author><author><name sortKey="Sakarellos Daitsiotis, Maria" sort="Sakarellos Daitsiotis, Maria" uniqKey="Sakarellos Daitsiotis M" first="Maria" last="Sakarellos-Daitsiotis">Maria Sakarellos-Daitsiotis</name></author><author><name sortKey="Tsikaris, Vassilios" sort="Tsikaris, Vassilios" uniqKey="Tsikaris V" first="Vassilios" last="Tsikaris">Vassilios Tsikaris</name></author><author><name sortKey="Sakarellos, Constantinos" sort="Sakarellos, Constantinos" uniqKey="Sakarellos C" first="Constantinos" last="Sakarellos">Constantinos Sakarellos</name></author><author><name sortKey="Marinou, Martha" sort="Marinou, Martha" uniqKey="Marinou M" first="Martha" last="Marinou">Martha Marinou</name></author><author><name sortKey="Thureau, Aurelien" sort="Thureau, Aurelien" uniqKey="Thureau A" first="Aurélien" last="Thureau">Aurélien Thureau</name></author><author><name sortKey="Cung, Manh Thong" sort="Cung, Manh Thong" uniqKey="Cung M" first="Manh Thong" last="Cung">Manh Thong Cung</name></author><author><name sortKey="Tzartos, Socrates J" sort="Tzartos, Socrates J" uniqKey="Tzartos S" first="Socrates J" last="Tzartos">Socrates J. Tzartos</name></author></analytic><series><title level="j">Biochemistry</title><idno type="ISSN">0006-2960</idno><imprint><date when="2003" type="published">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antibodies, Monoclonal (chemistry)</term><term>Antibodies, Monoclonal (metabolism)</term><term>Binding Sites</term><term>Binding, Competitive</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Humans</term><term>Ion Channels (antagonists & inhibitors)</term><term>Models, Molecular</term><term>Nuclear Magnetic Resonance, Biomolecular</term><term>Peptides (chemistry)</term><term>Peptides (genetics)</term><term>Peptides (pharmacology)</term><term>Phosphorylation</term><term>Protein Conformation</term><term>Protein Subunits</term><term>Radioimmunoassay</term><term>Receptors, Nicotinic (chemistry)</term><term>Receptors, Nicotinic (genetics)</term><term>Receptors, Nicotinic (metabolism)</term><term>Solutions</term><term>Structure-Activity Relationship</term><term>Torpedo (metabolism)</term><term>Tyrosine (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps monoclonaux ()</term><term>Anticorps monoclonaux (métabolisme)</term><term>Canaux ioniques (antagonistes et inhibiteurs)</term><term>Conformation des protéines</term><term>Dosage radioimmunologique</term><term>Fixation compétitive</term><term>Humains</term><term>Modèles moléculaires</term><term>Peptides ()</term><term>Peptides (génétique)</term><term>Peptides (pharmacologie)</term><term>Phosphorylation</term><term>Relation structure-activité</term><term>Récepteurs nicotiniques ()</term><term>Récepteurs nicotiniques (génétique)</term><term>Récepteurs nicotiniques (métabolisme)</term><term>Résonance magnétique nucléaire biomoléculaire</term><term>Sites de fixation</term><term>Solutions</term><term>Sous-unités de protéines</term><term>Séquence d'acides aminés</term><term>Test ELISA</term><term>Torpedo (métabolisme)</term><term>Tyrosine (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Ion Channels</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Peptides</term><term>Receptors, Nicotinic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Peptides</term><term>Receptors, Nicotinic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Receptors, Nicotinic</term><term>Tyrosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Canaux ioniques</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Peptides</term><term>Récepteurs nicotiniques</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Torpedo</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Anticorps monoclonaux</term><term>Récepteurs nicotiniques</term><term>Torpedo</term><term>Tyrosine</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Peptides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Binding Sites</term><term>Binding, Competitive</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Humans</term><term>Models, Molecular</term><term>Nuclear Magnetic Resonance, Biomolecular</term><term>Phosphorylation</term><term>Protein Conformation</term><term>Protein Subunits</term><term>Radioimmunoassay</term><term>Solutions</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Anticorps monoclonaux</term><term>Conformation des protéines</term><term>Dosage radioimmunologique</term><term>Fixation compétitive</term><term>Humains</term><term>Modèles moléculaires</term><term>Peptides</term><term>Phosphorylation</term><term>Relation structure-activité</term><term>Récepteurs nicotiniques</term><term>Résonance magnétique nucléaire biomoléculaire</term><term>Sites de fixation</term><term>Solutions</term><term>Sous-unités de protéines</term><term>Séquence d'acides aminés</term><term>Test ELISA</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Phosphorylation of the acetylcholine receptor (AChR) seems to be responsible for triggering several effects including its desensitization and aggregation at the postsynaptic membrane and probably initiates a signal transduction pathway at the postsynaptic membrane. To study the structural and functional role of the tyrosine phosphorylation site of the AChR beta-subunit and contribute to the in-depth understanding of the structural basis of the ion channel function, we synthesized four peptides containing the phosphorylated and nonphosphorylated sequences (380-391) of the human and Torpedo AChR beta-subunits and studied their interaction with a monoclonal antibody (mAb 148) that is known to bind to this region and that is capable of blocking ion channel function. All four peptides were efficient inhibitors of mAb 148 binding to AChR, although the nonphosphorylated human peptide was considerably less effective than the three others. We then investigated the conformation acquired by all four peptides in their antibody-bound state, which possibly illustrates the local conformation of the corresponding sites on the intact AChR molecule. The phosphorylated human and Torpedo peptides adopted a distorted 3(10) helix conformation. The nonphosphorylated Torpedo peptide, which is also an efficient inhibitor, was also folded. In contrast, the nonphosphorylated human peptide (a less efficient inhibitor) presented an extended structure. It is concluded that the phosphorylation of the AChR at its beta-subunit Tyr site leads to a significant change in its conformation, which may affect several functions of the AChR.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Grand Est</li><li>Lorraine (région)</li></region><settlement><li>Nancy</li></settlement></list><tree><noCountry><name sortKey="Cung, Manh Thong" sort="Cung, Manh Thong" uniqKey="Cung M" first="Manh Thong" last="Cung">Manh Thong Cung</name><name sortKey="Hemmerlin, Christine" sort="Hemmerlin, Christine" uniqKey="Hemmerlin C" first="Christine" last="Hemmerlin">Christine Hemmerlin</name><name sortKey="Krikorian, Dimitrios" sort="Krikorian, Dimitrios" uniqKey="Krikorian D" first="Dimitrios" last="Krikorian">Dimitrios Krikorian</name><name sortKey="Marinou, Martha" sort="Marinou, Martha" uniqKey="Marinou M" first="Martha" last="Marinou">Martha Marinou</name><name sortKey="Sakarellos Daitsiotis, Maria" sort="Sakarellos Daitsiotis, Maria" uniqKey="Sakarellos Daitsiotis M" first="Maria" last="Sakarellos-Daitsiotis">Maria Sakarellos-Daitsiotis</name><name sortKey="Sakarellos, Constantinos" sort="Sakarellos, Constantinos" uniqKey="Sakarellos C" first="Constantinos" last="Sakarellos">Constantinos Sakarellos</name><name sortKey="Thureau, Aurelien" sort="Thureau, Aurelien" uniqKey="Thureau A" first="Aurélien" last="Thureau">Aurélien Thureau</name><name sortKey="Tsikaris, Vassilios" sort="Tsikaris, Vassilios" uniqKey="Tsikaris V" first="Vassilios" last="Tsikaris">Vassilios Tsikaris</name><name sortKey="Tzartos, Socrates J" sort="Tzartos, Socrates J" uniqKey="Tzartos S" first="Socrates J" last="Tzartos">Socrates J. Tzartos</name></noCountry><country name="France"><region name="Grand Est"><name sortKey="Phan Chan Du, Angelique" sort="Phan Chan Du, Angelique" uniqKey="Phan Chan Du A" first="Angélique" last="Phan-Chan-Du">Angélique Phan-Chan-Du</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Lorraine/explor/LrgpV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001638 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001638 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Lorraine
|area= LrgpV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:12809492
|texte= Solution conformation of the antibody-bound tyrosine phosphorylation site of the nicotinic acetylcholine receptor beta-subunit in its phosphorylated and nonphosphorylated states.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:12809492" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a LrgpV1
| This area was generated with Dilib version V0.6.32. |  |