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rdf:type |
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lifeskim:mentions |
umls-concept:C0064847,
umls-concept:C0086376,
umls-concept:C0205251,
umls-concept:C0229304,
umls-concept:C0392747,
umls-concept:C1334350,
umls-concept:C1442792,
umls-concept:C1510827,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1879547
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pubmed:issue |
42
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pubmed:dateCreated |
2003-10-13
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pubmed:abstractText |
Recent studies have revealed that G-protein-coupled receptors contain a putative cytoplasmic helical domain, helix 8. Leukotriene B4 (LTB4) receptor 1 derivatives with truncated or mutated helix 8 showed much higher LTB4 binding than wild-type (WT) receptors. Similar to the WT receptor, LTB4 promoted guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding in these mutants. Unlike the WT receptor, however, the addition of GTPgammaS did not inhibit LTB4 binding to the mutant receptors. Scatchard analyses revealed that mutants maintained high affinity for LTB4, even in the presence of excess GTPgammaS. Consistently, mutant receptors showed a more prolonged Ca2+ mobilization and cellular metabolic activation than the WT receptor. From mutational studies and three-dimensional modeling based on the structure of bovine rhodopsin, we conclude that the helix 8 of LTB4 receptor 1 plays an important role in the conformational change of the receptor to the low affinity state after G-protein activation, possibly by sensing the status of coupling Galpha subunits as GTP-bound.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
41500-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12902330-Amino Acid Sequence,
pubmed-meshheading:12902330-Animals,
pubmed-meshheading:12902330-Blotting, Western,
pubmed-meshheading:12902330-Calcium,
pubmed-meshheading:12902330-Cattle,
pubmed-meshheading:12902330-Cell Line,
pubmed-meshheading:12902330-Cell Membrane,
pubmed-meshheading:12902330-Cytoplasm,
pubmed-meshheading:12902330-DNA Mutational Analysis,
pubmed-meshheading:12902330-Dose-Response Relationship, Drug,
pubmed-meshheading:12902330-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:12902330-Flow Cytometry,
pubmed-meshheading:12902330-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:12902330-Guanosine Triphosphate,
pubmed-meshheading:12902330-Humans,
pubmed-meshheading:12902330-Immunohistochemistry,
pubmed-meshheading:12902330-Kinetics,
pubmed-meshheading:12902330-Ligands,
pubmed-meshheading:12902330-Microscopy, Fluorescence,
pubmed-meshheading:12902330-Models, Molecular,
pubmed-meshheading:12902330-Molecular Sequence Data,
pubmed-meshheading:12902330-Mutagenesis,
pubmed-meshheading:12902330-Mutagenesis, Site-Directed,
pubmed-meshheading:12902330-Mutation,
pubmed-meshheading:12902330-Protein Binding,
pubmed-meshheading:12902330-Protein Conformation,
pubmed-meshheading:12902330-Receptors, Leukotriene B4,
pubmed-meshheading:12902330-Rhodopsin,
pubmed-meshheading:12902330-Sequence Homology, Amino Acid,
pubmed-meshheading:12902330-Transfection
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pubmed:year |
2003
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pubmed:articleTitle |
Helix 8 of the leukotriene B4 receptor is required for the conformational change to the low affinity state after G-protein activation.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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