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==Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels==
<StructureSection load='1wxn' size='340' side='right'caption='[[1wxn]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1wxn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Anthopleura_elegantissima Anthopleura elegantissima]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WXN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WXN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 25 models</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=1wxn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wxn OCA], [https://pdbe.org/1wxn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wxn RCSB], [https://www.ebi.ac.uk/pdbsum/1wxn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wxn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BDS2_ANTEL BDS2_ANTEL] This toxin potently blocks acid-sensing ion channel ASIC3 homotrimers and heterotrimers containing ASIC3 (composed with isoforms of ASIC1 and ASIC2) (PubMed:15044953). It also weakly inhibits potassium channels, and sodium channels (PubMed:15044953, PubMed:21943094, PubMed:22972919, PubMed:25337890). On homomeric ASIC3, this protein shows IC(50)=57-87 nM on rat, 37.3 nM on mouse and 175 nM on human channels (PubMed:15044953, PubMed:18923424, PubMed:19306891, PubMed:20813121, PubMed:21943094, PubMed:22851922, PubMed:22851929). The blockade is rapid and reversible (PubMed:15044953). On heterotrimeric forms, the toxin is less potent (IC(50)=117 nM on rat ASIC2b-ASIC3 channel, 900 nM on rat ASIC1b-ASIC3, and 2 uM on rat ASIC1a-ASIC3) (PubMed:15044953). It weakly inhibits Kv3.4/KCNC4 potassium channels (3 uM of the toxin inhibits 38% of Kv3.4 current) (PubMed:15044953). It reversibly and voltage-dependently inhibits hKv11.1/KCNH2/ERG1 potassium channels (IC(50)=1.21 uM), inhibiting both peak and tail currents without action on channel inactivation (PubMed:25337890). It weakly inhibits rNav1.2/SCN2A (EC(50)=114 nM), rNav1.6/SCN8A current (17% at 1 uM of the toxin) and Nav1.8/SCN10A (IC(50)=6.6 uM on human channels expressed in oocytes, EC(50)=55 nM on rat channels expressed in oocytes, and 2.6 uM on rat channels in DRG neurons) (PubMed:21943094, PubMed:22972919). It may act on sodium channels by binding at site 1 or close by, when the pore is in an open configuration (PubMed:22972919). In vivo, central injection does not induce neurotoxin symptoms in mice even after 24 hours (PubMed:15044953). However, it abolishes acid-induced pain in rats (PubMed:18923424).<ref>PMID:15044953</ref> <ref>PMID:18923424</ref> <ref>PMID:19306891</ref> <ref>PMID:20813121</ref> <ref>PMID:21943094</ref> <ref>PMID:22851922</ref> <ref>PMID:22851929</ref> <ref>PMID:22972919</ref> <ref>PMID:25337890</ref> 
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== Publication Abstract from PubMed ==
Acid-sensing ion channels (ASIC) are proton-gated sodium channels that have been implicated in pain transduction associated with acidosis in inflamed or ischemic tissues. APETx2, a peptide toxin effector of ASIC3, has been purified from an extract of the sea anemone Anthopleura elegantissima. APETx2 is a 42-amino-acid peptide cross-linked by three disulfide bridges. Its three-dimensional structure, as determined by conventional two-dimensional 1H-NMR, consists of a compact disulfide-bonded core composed of a four-stranded beta-sheet. It belongs to the disulfide-rich all-beta structural family encompassing peptide toxins commonly found in animal venoms. The structural characteristics of APETx2 are compared with that of PcTx1, another effector of ASIC channels but specific to the ASIC1a subtype and to APETx1, a toxin structurally related to APETx2, which targets the HERG potassium channel. Structural comparisons, coupled with the analysis of the electrostatic characteristics of these various ion channel effectors, led us to suggest a putative channel interaction surface for APETx2, encompassing its N terminus together with the type I-beta turn connecting beta-strands III and IV. This basic surface (R31 and R17) is also rich in aromatic residues (Y16, F15, Y32, and F33). An additional region made of the type II'-beta turn connecting beta-strands I and II could also play a role in the specificity observed for these different ion effectors.

Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels.,Chagot B, Escoubas P, Diochot S, Bernard C, Lazdunski M, Darbon H Protein Sci. 2005 Aug;14(8):2003-10. Epub 2005 Jun 29. PMID:15987885<ref>PMID:15987885</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Anthopleura elegantissima]]
[[Category: Large Structures]]
[[Category: Bernard C]]
[[Category: Chagot B]]
[[Category: Darbon H]]
[[Category: Diochot S]]
[[Category: Escoubas P]]
[[Category: Lazdunski M]]