2pzx: Difference between revisions
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==Structure of the methuselah ectodomain with peptide inhibitor== | ==Structure of the methuselah ectodomain with peptide inhibitor== | ||
<StructureSection load='2pzx' size='340' side='right' caption='[[2pzx]], [[Resolution|resolution]] 3.50Å' scene=''> | <StructureSection load='2pzx' size='340' side='right' caption='[[2pzx]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fjr|1fjr]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fjr|1fjr]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mth ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mth ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pzx OCA], [http://pdbe.org/2pzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pzx RCSB], [http://www.ebi.ac.uk/pdbsum/2pzx PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pzx OCA], [http://pdbe.org/2pzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pzx RCSB], [http://www.ebi.ac.uk/pdbsum/2pzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2pzx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pzx ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
Revision as of 12:35, 18 October 2017
Structure of the methuselah ectodomain with peptide inhibitorStructure of the methuselah ectodomain with peptide inhibitor
Structural highlights
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.[1] [2] 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 PubMedG 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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