2pzx

Structure of the methuselah ectodomain with peptide inhibitorStructure of the methuselah ectodomain with peptide inhibitor

Structural highlights 2pzx is a 4 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MTH_DROME Involved in biological aging and stress response. Essential for adult survival. Required in the presynaptic motor neuron to up-regulate neurotransmitter exocytosis at larval glutamatergic neuromuscular junctions (NMJs). Regulates a step associated with docking and clustering of vesicles at release sites. Sun, Acp70A/SP and eys/SPAM are agonists that activate mth. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 2pzx, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image