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2pzx

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Structure 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.^[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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pzx"

@@ Line 3: / Line 3: @@
 <StructureSection load='2pzx' size='340' side='right'caption='[[2pzx]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == 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]] 3.5&#8491;</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>
 <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>
 == 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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 32: @@
 __TOC__
 </StructureSection>
-[[Category: Drome]]
+[[Category: Drosophila melanogaster]]
 [[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]]

2pzx

From Proteopedia

Current revision

Structure of the methuselah ectodomain with peptide inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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