Source:http://linkedlifedata.com/resource/pubmed/id/18467541
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2008-7-23
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| pubmed:abstractText |
The amino terminus of class II G protein-coupled receptors plays an important role in ligand binding and receptor activation. Understanding of the conformation of the amino-terminal domain of these receptors has been substantially advanced with the solution of nuclear magnetic resonance and crystal structures of this region of receptors for corticotrophin-releasing factor, pituitary adenylate cyclase-activating polypeptide, and gastric inhibitory polypeptide. However, the orientation of the amino terminus relative to the receptor core and how the receptor gets activated upon ligand binding remain unclear. In this work, we have used photoaffinity labeling to identify a critical spatial approximation between residue five of secretin and a residue within the proposed third extracellular loop of the secretin receptor. This was achieved by purification, deglycosylation, cyanogen bromide cleavage, and sequencing of labeled wild-type and mutant secretin receptors. This constraint has been used to refine our evolving molecular model of secretin docked at the intact receptor, which for the first time includes refined helical bundle and loop regions and reflects a peptide-binding groove within the receptor amino terminus that directs the amino terminus of the peptide toward the receptor body. This model is fully consistent with the endogenous agonist mechanism for class II G protein-coupled receptor activation, where ligand binding promotes the interaction of a portion of the receptor amino terminus with the receptor body to activate it.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Photoaffinity Labels,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Gastrointestinal Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Secretin,
http://linkedlifedata.com/resource/pubmed/chemical/secretin receptor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1521-0111
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
74
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
413-22
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| pubmed:meshHeading |
pubmed-meshheading:18467541-Amino Acid Sequence,
pubmed-meshheading:18467541-Animals,
pubmed-meshheading:18467541-CHO Cells,
pubmed-meshheading:18467541-COS Cells,
pubmed-meshheading:18467541-Cercopithecus aethiops,
pubmed-meshheading:18467541-Cricetinae,
pubmed-meshheading:18467541-Cricetulus,
pubmed-meshheading:18467541-Models, Molecular,
pubmed-meshheading:18467541-Molecular Sequence Data,
pubmed-meshheading:18467541-Photoaffinity Labels,
pubmed-meshheading:18467541-Protein Binding,
pubmed-meshheading:18467541-Protein Conformation,
pubmed-meshheading:18467541-Protein Structure, Secondary,
pubmed-meshheading:18467541-Protein Structure, Tertiary,
pubmed-meshheading:18467541-Rats,
pubmed-meshheading:18467541-Receptors, G-Protein-Coupled,
pubmed-meshheading:18467541-Receptors, Gastrointestinal Hormone,
pubmed-meshheading:18467541-Secretin,
pubmed-meshheading:18467541-Sequence Homology, Amino Acid
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| pubmed:year |
2008
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| pubmed:articleTitle |
Spatial approximation between secretin residue five and the third extracellular loop of its receptor provides new insight into the molecular basis of natural agonist binding.
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| pubmed:affiliation |
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, AZ 85259, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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