2pzx
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| , resolution 3.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | mth (Drosophila melanogaster) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of the methuselah ectodomain with peptide inhibitor
OverviewOverview
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.
About this StructureAbout this Structure
2PZX is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.
ReferenceReference
Extension of Drosophila melanogaster life span with a GPCR peptide inhibitor., Ja WW, West AP Jr, Delker SL, Bjorkman PJ, Benzer S, Roberts RW, Nat Chem Biol. 2007 Jul;3(7):415-9. Epub 2007 Jun 3. PMID:17546039
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