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rdf:type |
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lifeskim:mentions |
umls-concept:C0013139,
umls-concept:C0030956,
umls-concept:C0376558,
umls-concept:C0439792,
umls-concept:C0682972,
umls-concept:C1367690,
umls-concept:C1426330,
umls-concept:C1428424,
umls-concept:C1711300,
umls-concept:C1999216,
umls-concept:C2700613
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pubmed:issue |
7
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pubmed:dateCreated |
2007-6-19
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pubmed:databankReference |
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pubmed:abstractText |
G protein-coupled receptors (GPCRs) mediate signaling from extracellular ligands to intracellular signal transduction proteins. Methuselah (Mth) is a class B (secretin-like) GPCR, a family typified by their large, ligand-binding, N-terminal extracellular domains. Downregulation of mth increases the life span of Drosophila melanogaster; inhibitors of Mth signaling should therefore enhance longevity. We used mRNA display selection to identify high-affinity (K(d) = 15 to 30 nM) peptide ligands that bind to the N-terminal ectodomain of Mth. The selected peptides are potent antagonists of Mth signaling, and structural studies suggest that they perturb the interface between the Mth ecto- and transmembrane domains. Flies constitutively expressing a Mth antagonist peptide have a robust life span extension, which suggests that the peptides inhibit Mth signaling in vivo. Our work thus provides new life span-extending ligands for a metazoan and a general approach for the design of modulators of this important class of GPCRs.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-10545918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-10835604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-10913300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-10926528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-10982894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-11239576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-11274391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-11790261,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-12196198,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-12367510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-12633996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-12711346,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-15133470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-15248784,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-15950876,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-15980016,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-16677788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-17064868,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-17168552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-17576421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-6289436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-7529940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-7979235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-8946950,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-9356443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-9584619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-9608508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17546039-9794765
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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 |
Jul
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pubmed:issn |
1552-4450
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
415-9
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:17546039-Amino Acid Sequence,
pubmed-meshheading:17546039-Animals,
pubmed-meshheading:17546039-Down-Regulation,
pubmed-meshheading:17546039-Drosophila Proteins,
pubmed-meshheading:17546039-Drosophila melanogaster,
pubmed-meshheading:17546039-Ligands,
pubmed-meshheading:17546039-Longevity,
pubmed-meshheading:17546039-Models, Molecular,
pubmed-meshheading:17546039-Molecular Sequence Data,
pubmed-meshheading:17546039-Peptide Library,
pubmed-meshheading:17546039-Peptides,
pubmed-meshheading:17546039-RNA, Messenger,
pubmed-meshheading:17546039-Receptors, G-Protein-Coupled,
pubmed-meshheading:17546039-Signal Transduction
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pubmed:year |
2007
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pubmed:articleTitle |
Extension of Drosophila melanogaster life span with a GPCR peptide inhibitor.
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pubmed:affiliation |
Division of Biology, 1200 E. California Blvd. 156-29, California Institute of Technology, Pasadena, California 91125, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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