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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5854
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pubmed:dateCreated |
2007-11-23
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pubmed:databankReference |
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pubmed:abstractText |
The beta2-adrenergic receptor (beta2AR) is a well-studied prototype for heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) that respond to diffusible hormones and neurotransmitters. To overcome the structural flexibility of the beta2AR and to facilitate its crystallization, we engineered a beta2AR fusion protein in which T4 lysozyme (T4L) replaces most of the third intracellular loop of the GPCR ("beta2AR-T4L") and showed that this protein retains near-native pharmacologic properties. Analysis of adrenergic receptor ligand-binding mutants within the context of the reported high-resolution structure of beta2AR-T4L provides insights into inverse-agonist binding and the structural changes required to accommodate catecholamine agonists. Amino acids known to regulate receptor function are linked through packing interactions and a network of hydrogen bonds, suggesting a conformational pathway from the ligand-binding pocket to regions that interact with G proteins.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Muramidase,
http://linkedlifedata.com/resource/pubmed/chemical/Propanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/carazolol
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1095-9203
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pubmed:author |
pubmed-author:CherezovVadimV,
pubmed-author:ChoiHee-JungHJ,
pubmed-author:HansonMichael AMA,
pubmed-author:KobilkaBrian KBK,
pubmed-author:KobilkaTong SunTS,
pubmed-author:RasmussenSøren G FSG,
pubmed-author:RosenbaumDaniel MDM,
pubmed-author:StevensRaymond CRC,
pubmed-author:ThianFoon SunFS,
pubmed-author:WeisWilliam IWI,
pubmed-author:YaoXiao-JieXJ
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pubmed:issnType |
Electronic
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pubmed:day |
23
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pubmed:volume |
318
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1266-73
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pubmed:meshHeading |
pubmed-meshheading:17962519-Adrenergic beta-Agonists,
pubmed-meshheading:17962519-Adrenergic beta-Antagonists,
pubmed-meshheading:17962519-Amino Acid Sequence,
pubmed-meshheading:17962519-Bacteriophage T4,
pubmed-meshheading:17962519-Binding Sites,
pubmed-meshheading:17962519-Cell Line,
pubmed-meshheading:17962519-Cell Membrane,
pubmed-meshheading:17962519-Crystallization,
pubmed-meshheading:17962519-Crystallography, X-Ray,
pubmed-meshheading:17962519-Drug Inverse Agonism,
pubmed-meshheading:17962519-Humans,
pubmed-meshheading:17962519-Immunoglobulin Fab Fragments,
pubmed-meshheading:17962519-Ligands,
pubmed-meshheading:17962519-Models, Molecular,
pubmed-meshheading:17962519-Molecular Sequence Data,
pubmed-meshheading:17962519-Muramidase,
pubmed-meshheading:17962519-Propanolamines,
pubmed-meshheading:17962519-Protein Conformation,
pubmed-meshheading:17962519-Protein Structure, Secondary,
pubmed-meshheading:17962519-Protein Structure, Tertiary,
pubmed-meshheading:17962519-Receptors, Adrenergic, beta-2,
pubmed-meshheading:17962519-Recombinant Fusion Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function.
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pubmed:affiliation |
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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