2pzx
From Proteopedia
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'''Structure of the methuselah ectodomain with peptide inhibitor''' | '''Structure of the methuselah ectodomain with peptide inhibitor''' | ||
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[[Category: Jr., A P.West.]] | [[Category: Jr., A P.West.]] | ||
[[Category: Roberts, R W.]] | [[Category: Roberts, R W.]] | ||
| - | [[Category: | + | [[Category: Gpcr g protein-coupled receptor ectodomain]] |
| - | [[Category: | + | [[Category: Signaling protein]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:05:03 2008'' | |
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Revision as of 11:05, 4 May 2008
Structure of the methuselah ectodomain with peptide inhibitor
Overview
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 Structure
2PZX is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sun May 4 14:05:03 2008
