7txf: Difference between revisions
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The | ==The allosteric binding mode of alphaD-conotoxin VxXXB== | ||
<StructureSection load='7txf' size='340' side='right'caption='[[7txf]], [[Resolution|resolution]] 2.47Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7txf]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_vexillum Conus vexillum] and [https://en.wikipedia.org/wiki/Lymnaea_stagnalis Lymnaea stagnalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TXF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.47Å</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=7txf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7txf OCA], [https://pdbe.org/7txf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7txf RCSB], [https://www.ebi.ac.uk/pdbsum/7txf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7txf ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
alphaD-conotoxins are 11 kDa homodimers that potently inhibit nicotinic acetylcholine receptors (nAChRs) through a non-competitive (allosteric) mechanism. In this study, we describe the allosteric binding mode of the granulin-like C-terminal (CTD) of VxXXB bound to Lymnea stagnalis acetylcholine binding protein (Ls-AChBP), a soluble homologue of the extracellular ligand-binding domain of nAChRs. This co-crystal complex revealed a novel allosteric binding site for nAChR antagonists outside the C-loop that caps the orthosteric site defined by the nAChR agonist nicotine and the antagonist epibatidine. Mutational and docking studies on Ls-AChBP supported a two-site binding mode for full-length VxXXB, with the first CTD binding site located outside the C-loop as seen in the co-crystal complex, with a second CTD binding site located near the N-terminal end of the adjacent subunit of AChBP. These results provide new structural insight into a novel allosteric mechanism of nAChR inhibition and define the cooperative binding mode of the N-terminal domain linked granulin core domains of alphaD-conotoxins. | |||
Unravelling the allosteric binding mode of alphaD-VxXXB at nicotinic acetylcholine receptors.,Ho TN, Abraham N, Lewis RJ Front Pharmacol. 2023 Apr 13;14:1170514. doi: 10.3389/fphar.2023.1170514. , eCollection 2023. PMID:37124228<ref>PMID:37124228</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7txf" style="background-color:#fffaf0;"></div> | ||
[[Category: Ho | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Conus vexillum]] | |||
[[Category: Large Structures]] | |||
[[Category: Lymnaea stagnalis]] | |||
[[Category: Abraham N]] | |||
[[Category: Ho TNT]] | |||
[[Category: Lewis RJ]] | |||
Latest revision as of 12:13, 17 October 2024
The allosteric binding mode of alphaD-conotoxin VxXXBThe allosteric binding mode of alphaD-conotoxin VxXXB
Structural highlights
Publication Abstract from PubMedalphaD-conotoxins are 11 kDa homodimers that potently inhibit nicotinic acetylcholine receptors (nAChRs) through a non-competitive (allosteric) mechanism. In this study, we describe the allosteric binding mode of the granulin-like C-terminal (CTD) of VxXXB bound to Lymnea stagnalis acetylcholine binding protein (Ls-AChBP), a soluble homologue of the extracellular ligand-binding domain of nAChRs. This co-crystal complex revealed a novel allosteric binding site for nAChR antagonists outside the C-loop that caps the orthosteric site defined by the nAChR agonist nicotine and the antagonist epibatidine. Mutational and docking studies on Ls-AChBP supported a two-site binding mode for full-length VxXXB, with the first CTD binding site located outside the C-loop as seen in the co-crystal complex, with a second CTD binding site located near the N-terminal end of the adjacent subunit of AChBP. These results provide new structural insight into a novel allosteric mechanism of nAChR inhibition and define the cooperative binding mode of the N-terminal domain linked granulin core domains of alphaD-conotoxins. Unravelling the allosteric binding mode of alphaD-VxXXB at nicotinic acetylcholine receptors.,Ho TN, Abraham N, Lewis RJ Front Pharmacol. 2023 Apr 13;14:1170514. doi: 10.3389/fphar.2023.1170514. , eCollection 2023. PMID:37124228[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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