| Coupling ligand structure to specific conformational switches in the beta2-adrenoceptor. | |
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MedLine Citation:
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PMID: 16799554 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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G protein-coupled receptors (GPCRs) regulate a wide variety of physiological functions in response to structurally diverse ligands ranging from cations and small organic molecules to peptides and glycoproteins. For many GPCRs, structurally related ligands can have diverse efficacy profiles. To investigate the process of ligand binding and activation, we used fluorescence spectroscopy to study the ability of ligands having different efficacies to induce a specific conformational change in the human beta2-adrenoceptor (beta2-AR). The 'ionic lock' is a molecular switch found in rhodopsin-family GPCRs that has been proposed to link the cytoplasmic ends of transmembrane domains 3 and 6 in the inactive state. We found that most partial agonists were as effective as full agonists in disrupting the ionic lock. Our results show that disruption of this important molecular switch is necessary, but not sufficient, for full activation of the beta2-AR. |
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Authors:
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Xiaojie Yao; Charles Parnot; Xavier Deupi; Venkata R P Ratnala; Gayathri Swaminath; David Farrens; Brian Kobilka |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-06-25 |
Journal Detail:
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Title: Nature chemical biology Volume: 2 ISSN: 1552-4450 ISO Abbreviation: Nat. Chem. Biol. Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-07-19 Completed Date: 2006-09-11 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 101231976 Medline TA: Nat Chem Biol Country: United States |
Other Details:
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Languages: eng Pagination: 417-22 Citation Subset: IM |
Affiliation:
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Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, Palo Alto, California 94305, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PubChem-Substance/11534307; 11534308; 11534309; 11534310; 11534311; 11534312; 11534313; 11534314; 11534315; 11534316 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Albuterol
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pharmacology Alprenolol / pharmacology Amino Acid Sequence Binding Sites Crystallography, X-Ray Epinephrine / pharmacology Humans Isoproterenol / pharmacology Ligands Models, Molecular Molecular Sequence Data Molecular Structure Propanolamines / pharmacology Protein Conformation / drug effects Protein Structure, Tertiary / drug effects Receptors, Adrenergic, beta-2 / agonists, chemistry*, metabolism* Sensitivity and Specificity Spectrometry, Fluorescence |
| Grant Support | |
ID/Acronym/Agency:
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5 R01 NS28471/NS/NINDS NIH HHS; R01 DA14896/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 0/Propanolamines; 0/Receptors, Adrenergic, beta-2; 13655-52-2/Alprenolol; 18559-94-9/Albuterol; 51-43-4/Epinephrine; 72795-19-8/ICI 118551; 7683-59-2/Isoproterenol |
| Comments/Corrections | |
Comment In:
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Nat Chem Biol. 2006 Aug;2(8):395-6
[PMID:
16850011
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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