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
