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| | <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=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2pzx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PZX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pzx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PZX FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fjr|1fjr]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mth ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pzx OCA], [https://pdbe.org/2pzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pzx RCSB], [https://www.ebi.ac.uk/pdbsum/2pzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pzx ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pzx OCA], [https://pdbe.org/2pzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pzx RCSB], [https://www.ebi.ac.uk/pdbsum/2pzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pzx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MTH_DROME 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.<ref>PMID:9794765</ref> <ref>PMID:12367510</ref>
| + | [https://www.uniprot.org/uniprot/MTH_DROME 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.<ref>PMID:9794765</ref> <ref>PMID:12367510</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Benzer, S]] | + | [[Category: Benzer S]] |
| - | [[Category: Bjorkman, P J]] | + | [[Category: Bjorkman PJ]] |
| - | [[Category: Delker, S L]] | + | [[Category: Delker SL]] |
| - | [[Category: Ja, W W]] | + | [[Category: Ja WW]] |
| - | [[Category: Roberts, R W]] | + | [[Category: Roberts RW]] |
| - | [[Category: West, A P]] | + | [[Category: West Jr AP]] |
| - | [[Category: Gpcr g protein-coupled receptor ectodomain]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| 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 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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin YJ, Seroude L, Benzer S. Extended life-span and stress resistance in the Drosophila mutant methuselah. Science. 1998 Oct 30;282(5390):943-6. PMID:9794765
- ↑ Song W, Ranjan R, Dawson-Scully K, Bronk P, Marin L, Seroude L, Lin YJ, Nie Z, Atwood HL, Benzer S, Zinsmaier KE. Presynaptic regulation of neurotransmission in Drosophila by the g protein-coupled receptor methuselah. Neuron. 2002 Sep 26;36(1):105-19. PMID:12367510
- ↑ Ja WW, West AP Jr, Delker SL, Bjorkman PJ, Benzer S, Roberts RW. Extension of Drosophila melanogaster life span with a GPCR peptide inhibitor. Nat Chem Biol. 2007 Jul;3(7):415-9. Epub 2007 Jun 3. PMID:17546039 doi:10.1038/nchembio.2007.2
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