4x9z: Difference between revisions
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''' | ==Dimeric conotoxin alphaD-GeXXA== | ||
<StructureSection load='4x9z' size='340' side='right' caption='[[4x9z]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4x9z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Conus_generalis Conus generalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X9Z FirstGlance]. <br> | |||
</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=4x9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x9z OCA], [http://pdbe.org/4x9z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x9z RCSB], [http://www.ebi.ac.uk/pdbsum/4x9z PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Nicotinic acetylcholine receptors (nAChRs) play essential roles in transmitting acetylcholine-mediated neural signals across synapses and neuromuscular junctions, and are also closely linked to various diseases and clinical conditions. Therefore, novel nAChR-specific compounds have great potential for both neuroscience research and clinical applications. Conotoxins, the peptide neurotoxins produced by cone snails, are a rich reservoir of novel ligands that target receptors, ion channels and transporters in the nervous system. From the venom of Conus generalis, we identified a novel dimeric nAChR-inhibiting alphaD-conotoxin GeXXA. By solving the crystal structure and performing structure-guided dissection of this toxin, we demonstrated that the monomeric C-terminal domain of alphaD-GeXXA, GeXXA-CTD, retains inhibitory activity against the alpha9alpha10 nAChR subtype. Furthermore, we identified that His7 of the rat alpha10 nAChR subunit determines the species preference of alphaD-GeXXA, and is probably part of the binding site of this toxin. These results together suggest that alphaD-GeXXA cooperatively binds to two inter-subunit interfaces on the top surface of nAChR, thus allosterically disturbing the opening of the receptor. The novel antagonistic mechanism of alphaD-GeXXA via a new binding site on nAChRs provides a valuable basis for the rational design of new nAChR-targeting compounds. | |||
Conotoxin alphaD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors.,Xu S, Zhang T, Kompella SN, Yan M, Lu A, Wang Y, Shao X, Chi C, Adams DJ, Ding J, Wang C Sci Rep. 2015 Sep 23;5:14261. doi: 10.1038/srep14261. PMID:26395518<ref>PMID:26395518</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4x9z" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Conus generalis]] | |||
[[Category: Adams, D]] | |||
[[Category: Ding, J]] | [[Category: Ding, J]] | ||
[[Category: Kompella, S]] | |||
[[Category: Wang, C]] | |||
[[Category: Xu, S]] | |||
[[Category: Zhang, T]] | [[Category: Zhang, T]] | ||
[[Category: | [[Category: Alpha-conotoxin]] | ||
[[Category: | [[Category: Gexxa]] | ||
[[Category: | [[Category: Homodimer]] | ||
[[Category: | [[Category: Nicotinic acetylcholine receptor]] | ||
[[Category: Toxin]] | |||
Revision as of 19:10, 2 December 2015
Dimeric conotoxin alphaD-GeXXADimeric conotoxin alphaD-GeXXA
Structural highlights
Publication Abstract from PubMedNicotinic acetylcholine receptors (nAChRs) play essential roles in transmitting acetylcholine-mediated neural signals across synapses and neuromuscular junctions, and are also closely linked to various diseases and clinical conditions. Therefore, novel nAChR-specific compounds have great potential for both neuroscience research and clinical applications. Conotoxins, the peptide neurotoxins produced by cone snails, are a rich reservoir of novel ligands that target receptors, ion channels and transporters in the nervous system. From the venom of Conus generalis, we identified a novel dimeric nAChR-inhibiting alphaD-conotoxin GeXXA. By solving the crystal structure and performing structure-guided dissection of this toxin, we demonstrated that the monomeric C-terminal domain of alphaD-GeXXA, GeXXA-CTD, retains inhibitory activity against the alpha9alpha10 nAChR subtype. Furthermore, we identified that His7 of the rat alpha10 nAChR subunit determines the species preference of alphaD-GeXXA, and is probably part of the binding site of this toxin. These results together suggest that alphaD-GeXXA cooperatively binds to two inter-subunit interfaces on the top surface of nAChR, thus allosterically disturbing the opening of the receptor. The novel antagonistic mechanism of alphaD-GeXXA via a new binding site on nAChRs provides a valuable basis for the rational design of new nAChR-targeting compounds. Conotoxin alphaD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors.,Xu S, Zhang T, Kompella SN, Yan M, Lu A, Wang Y, Shao X, Chi C, Adams DJ, Ding J, Wang C Sci Rep. 2015 Sep 23;5:14261. doi: 10.1038/srep14261. PMID:26395518[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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